Genetic hypermutability of plants for gene discovery and diagnosis

ABSTRACT

The invention provides methods for identifying polymorphic markers for herbicide resistance in weeds and for generating herbicide susceptible and herbicide resistant weeds by mutagenizing weeds and comparing genetic differences between herbicide resistant and herbicide susceptible weeds. The methods may involve the inhibition of mismatch repair in the weeds through the introduction of dominant negative alleles of mismatch repair genes, through T-DNA insertional mutations, or the use of chemical inhibitors of mismatch repair. The invention also provides polymorphic markers of herbicide resistance and methods and kits to screen for herbicide resistant weeds, such as horseweed, goosegrass and rye grass.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. ProvisionalApplication Serial No. 60/328,750 filed Oct. 12, 2001, the disclosure ofwhich is hereby incorporated by reference in its entirety.

BACKGROUND OF INVENTION

[0002] 1. Field of the Invention

[0003] This invention relates to the field of genetic isolation andmanipulation of weeds and gene targets for the discovery of herbicidetolerant weeds. In particular, it relates to the discovery of genesessential for herbicide tolerance.

[0004] 2. Background of the Related Art

[0005] Herbicide use for crop management is a critical factor forfarmers to generate and maintain healthy, productive crops during thegrowing season in order to achieve maximal economic value from theirharvest. Several studies have found an association with the long-termuse of a single herbicide and the emergence of resistant weeds to thatparticular class or type of herbicide, thereby making the risk ofdecreased crop yields high (DeFelice, M. (1998) “Managing WeedResistance to Herbicides” Crop Insights, Vol. 8, No. 7). Herbicideresistance in weeds is conceptually no different from the generation ofantibiotic resistance that infectious microbes develop over the courseof long-term treatment in livestock and man. In plants, a majority ofweeds are typically killed by herbicide treatment, however, through theprocess of natural selection, genetic variants that are naturallyresistant to the toxic effects of an herbicide are enriched for, andeventually establish, a significant population of plants that can overgrow a field where herbicide treatment is the major source for weedmanagement (Jasieniuk, M. and B. D. Maxwell (1994) “Population geneticsand the evolution of herbicide resistance in weeds” Phytoprotection75(Suppl.):25-35).

[0006] Over the past decade, numerous reports have documented theemergence of herbicide-resistant weed populations. The first report ofherbicide resistant weeds was documented in 1968, which cited theemergence of strains resistant to triazine-based herbicides. By the year1991, over 120 weed biotypes have been identified that are resistant totriazine-based herbicides along with the emergence of resistant weeds tomore than 15 different herbicide classes throughout the world. As of1998, more than 195 herbicide resistant weeds have been reportedworldwide, highlighting a trend that parallels herbicide usage. Whilethere are clearly many benefits to using herbicide resistant crops, amajor disadvantage is the potential emergence of herbicide resistantweeds due to the over-reliance of a single herbicide or closely relatedclass of herbicides.

[0007] Many weed specialists throughout the world support the notionthat there will likely be an increase in the development of herbicideresistant (HR) weeds or at least a shift in tolerant weed populations asa result of overusing individual herbicides. In the United States,glyphosate resistant (GR) weeds are expected to pose a significantemergence due to the increased use of Roundup Ready® crops like cottonand soybeans, which have seen an explosion of acreage increases acrossthe country. While resistance to non-selective herbicides like Roundup®is thought to occur less rapidly than selective herbicides used in thepast, the emergence of GR weeds has already been reported in severaltypes of ryegrass and winter annual weeds, supporting the notion thatRoundup® resistant weeds may pose a serious problem for farmers usingRoundup Ready® crops in no-till, narrow-spaced crop management systems(Dyer, W. E. (1994) “Resistance to glyphosate” in Herbicide, S. B.Powles and J. A. M. Holtum, eds. Lewis Publishers, Boca Raton, Fla.,pp229-241; Hartzler, B. (1998) “Roundup resistant rigid ryegrass” IowaState University Weed Science Online,(www.weeds.iastate.edu/weednews/rigidryegrass.htm.).

[0008] Current methods to identify weed biotype use morphologicalcriteria for classification. Unfortunately, the mere morphology of aweed at the vegetative stage is practically impossible to determine a GRfrom a glyphosate-susceptible biotype (Wilbur Mountain, Weed Specialist,PA Dept. of Agriculture, personal communication). Genetic analysis inplants through mutagenesis techniques has been hampered by the inabilityto generate non-biased genome-wide mutations. Thus, there exists a needin the art for methods of determining the genes responsible forherbicide resistance and susceptibility, for effective screening methodsto identify herbicide resistant and susceptible plants in the field, andfor methods of altering the genotype of herbicide resistant weeds.

SUMMARY OF THE INVENTION

[0009] The invention provides methods for identifying polymorphicmarkers of herbicide resistance in a plant comprising: (a) isolatinggenomic DNA from an herbicide susceptible plant and an herbicideresistant plant of the same species; (b) performing genetic analysis onthe genomic DNA of the an herbicide susceptible plant and the herbicideresistant plant; and (c) identifying differences between the genomic DNAof the herbicide susceptible plant and the herbicide resistant plant,(d) identifying the differences that correlate with herbicide resistanceor herbicide susceptibility by screening samples of herbicide resistantand herbicide susceptible plants; thereby identifying polymorphicmarkers of herbicide resistance in the plant.

[0010] In some embodiments of the method of the invention, thepolymorphic markers comprise polynucleotide microsatellite markers whereherbicide resistant plants have a distinct haplotype pattern incomparison to herbicide susceptible species.

[0011] In some embodiments of the method of the invention, the plant isConyza canadensis. In other embodiments, the plant is Lolium rigidum. Inother embodiments, the plant is a goosegrass species.

[0012] In some embodiments of the method of the invention, the herbicidecomprises glyphosate. In other embodiments, the herbicide comprisesparaquot. In other embodiments, the herbicide comprises sulfonyl ureamoities.

[0013] The invention also provides methods for generating herbicidesusceptible weeds from herbicide resistant weeds comprising: (a)mutagenizing the resistant weeds, thereby creating mutant parentalweeds; (b) testing progeny of the mutant parental weeds forsusceptibility to the herbicide; and (c) selecting the mutant parentalweeds producing herbicide susceptible progeny. In addition, theinvention provides methods for generating herbicide resistant weeds fromherbicide susceptible weeds comprising: (a) mutagenizing the susceptibleweeds, thereby creating mutant parental weeds; (b) testing progeny ofthe mutant parental weeds for resistance to the herbicide; and (c)selecting the mutant parental weeds producing herbicide resistantprogeny.

[0014] In some embodiments of the method of the invention, the step oftesting comprises analyzing the progeny for resistance to an herbicideselected from the group consisting of aminoglycosides,5-enolpyruvylshikimate-3-phosphate synthase inhibitors, triazine-basedherbicides, beta-lactams, macrolides, lincosamides, sulfonamides,atrazine, alachlor, isoniazids, and metribuzin.

[0015] In certain embodiments, the invention provides a method forgenerating genetically stable glyphosate susceptible weeds derived fromglyphosate resistant parental weeds comprising: (a) contacting theglyphosate susceptible weed with an inhibitor of mismatch repair,thereby forming a hypermutable parental weed; (b) testing progeny of thehypermutable parental weed that are glyphosate susceptible; (c)selecting hypermutable parental strains producing glyphosate susceptibleprogeny; (d) removing the inhibitor of mismatch repair from thehypermutable parental weed, thereby making the hypermutable parentalweed genetically stable; and (e) obtaining progeny from geneticallystable parental weed.

[0016] In some embodiments of the method of the invention, the step ofmutagenizing is accomplished by introducing into the herbicide resistantweed a dominant negative allele of a mismatch repair gene. In someembodiments, the dominant negative allele of a mismatch gene is adominant negative allele of a gene encoding a mismatch repair proteinselected from the group consisting of PMS2, PMS1, MLH1, MSH2, MSH6,PMSR2, PMSR3, and PMSL9.

[0017] The mismatch repair allele may be derived from any organism,including, but not limited to mouse, human, Arabidopsis, Saccharomyces,and Oryza. In some embodiments, the dominant negative allele is a PMS2truncation mutant, such as, but not limited to a PMS2-134 mutant.

[0018] In other embodiments of the method of the invention, the step ofmutagenizing is accomplished by introducing into the herbicide resistantweed a chemical inhibitor of mismatch repair selected from the groupconsisting of an anthracene, an ATPase inhibitor, a nuclease inhibitor,a polymerase inhibitor and an antisense oligonucleotide thatspecifically hybridizes to a nucleotide encoding a mismatch repairprotein dominant negative allele of a mismatch repair gene. In someembodiments, the chemical inhibitor is an anthracene having the formula:

[0019] wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino,alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl,substituted alkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl,N-alkenyl, O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl,aryloxy, substituted aryloxy, heteroaryl, substituted heteroaryl,aralkyloxy, arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl,alkylsulfonyl, alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, analcohol, an amino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehydegroup, an ester, an ether, a crown ether, a ketone, an organosulfurcompound, an organometallic group, a carboxylic acid, an organosiliconor a carbohydrate that optionally contains one or more alkylatedhydroxyl groups; wherein the heteroalkyl, heteroaryl, and substitutedheteroaryl contain at least one heteroatom that is oxygen, sulfur, ametal atom, phosphorus, silicon or nitrogen; and wherein thesubstituents of the substituted alkyl, substituted alkenyl, substitutedalkynyl, substituted aryl, and substituted heteroaryl are halogen, CN,NO₂, lower alkyl, aryl, heteroaryl, aralkyl, aralkoxy, guanidino,alkoxycarbonyl, alkoxy, hydroxy, carboxy and amino; and wherein theamino groups are optionally substituted with an acyl group, or 1 to 3aryl or lower alkyl groups. In certain embodiments, R₅ and R₆ arehydrogen. In other embodiments, R₁-R₁₀ are independently hydrogen,hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl,tolyl, hydroxymethyl, hydroxypropyl, or hydroxybutyl.

[0020] In specific embodiments, the anthracene derivatives include, butare not limited to 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.

[0021] In other embodiments of the method of the invention, the step ofmutagenizing is accomplished using T-DNA insertional mutagenesis.

[0022] The invention also provides a method for identifying a mutantgene conferring herbicide resistance. In some embodiments, the methodcomprises: (a) comparing the genome of a naturally occurring herbicideresistant plant to the genome of an herbicide susceptible plant; (b)determining genetic differences between the herbicide resistant plant tothe herbicide susceptible plant; and (c) sequencing a region of DNAcomprising the genetic difference.

[0023] In other embodiments, the method comprises: (a) introducing intoan herbicide susceptible weed gene fragments from an herbicide resistantweed, thereby creating a transfected herbicide susceptible strain; (b)screening progeny of the transfected herbicide susceptible strain forherbicide resistance; and (c) sequencing the gene fragment to identifyan herbicide resistance gene.

[0024] In other embodiments, the method comprises: (a) introducing intoan herbicide resistant weed gene fragments from an herbicide susceptibleweed, thereby creating a transfected herbicide resistant strain; (b)screening progeny of the transfected herbicide resistant strain forherbicide susceptibility; and (c) sequencing the gene fragment toidentify an herbicide susceptibility gene.

[0025] In still other embodiments, the method comprises: (a) crossing anherbicide resistant weed with an herbicide susceptible weed, therebycreating a crossed strain; (b) screening progeny for herbicidesusceptibility; and (c) performing genetic analysis on the crossedstrain producing herbicide susceptible progeny to identify an herbicidesusceptibility gene.

[0026] In still other embodiments, the method comprises: (a) crossing anherbicide resistant weed with an herbicide susceptible weed, therebycreating a crossed strain; (b) screening progeny for herbicideresistance; and (c) performing genetic analysis on the crossed strainproducing herbicide resistant progeny to identify an herbicideresistance gene.

[0027] In the embodiments of the methods of the invention, the genome ofthe herbicide resistant plant and the genome of the herbicidesusceptible plant are compared by a technique which may include, but isnot limited to microarray analysis, genotyping of repetitive sequencesusing microsatellite markers to identify linked genomic segments thatare associated with a particular trait, single nucleotide polymorphic(SNP) analysis, restriction fragment length polymorphism (RFLP)analysis, amplified fragment length polymorphism (AFLP) analysis, simplesequence length polymorphism analysis (SSLPs), randomly amplifiedpolymorphic DNAs (RAPDs), DNA amplification fingerprinting (DAF),sequence characterized amplified regions (SCARs), arbitrary primedpolymerase chain reaction (AP-PCR), and single nucleotide polymorphisms(SNPs).

[0028] In the methods involving breeding of herbicide susceptible andherbicide resistant weeds, the method may further comprise a step ofperforming at least one backcross of the progeny with the crossedstrain.

[0029] The invention also provides methods for identifying a mutant geneconferring herbicide resistance. In some embodiments, the methodcomprises: (a) mutagenizing an herbicide susceptible weed, therebycreating mutant parental weeds; (b) testing progeny of the mutantparental weeds for resistance to the herbicide; (c) comparing the genomeof a naturally occurring herbicide resistant plant to the genome of anherbicide susceptible plant; (d) determining genetic differences betweenthe herbicide resistant plant to the herbicide susceptible plant; and(e) sequencing a region of DNA comprising the genetic difference.

[0030] In other embodiments, the method comprises: (a) mutagenizing anherbicide resistant weed, thereby creating mutant parental weeds; (b)testing progeny of the mutant parental weeds for susceptibility to theherbicide; (c) comparing the genome of a naturally occurring herbicideresistant plant to the genome of an herbicide susceptible plant; (d)determining genetic differences between the herbicide resistant plant tothe herbicide susceptible plant; and (e) sequencing a region of DNAcomprising the genetic difference.

[0031] In some embodiments of the method of the invention, the step ofmutagenizing is accomplished by introducing into the herbicide resistantweed a dominant negative allele of a mismatch repair gene. In someembodiments, the dominant negative allele of a mismatch gene is adominant negative allele of a gene encoding a mismatch repair proteinselected from the group consisting of PMS2, PMS 1, MLH1, MSH2, MSH6,PMSR2, PMSR3, and PMSL9. The mismatch repair allele may be derived fromany organism, including, but not limited to mouse, human, Arabidopsis,Saccharomyces, and Oryza. In some embodiments, the dominant negativeallele is a PMS2 truncation mutant, such as, but not limited to aPMS2-134 mutant.

[0032] In other embodiments of the method of the invention, the step ofmutagenizing is accomplished by introducing into the herbicide resistantweed a chemical inhibitor of mismatch repair selected from the groupconsisting of an anthracene, an ATPase inhibitor, a nuclease inhibitor,a polymerase inhibitor and an antisense oligonucleotide thatspecifically hybridizes to a nucleotide encoding a mismatch repairprotein dominant negative allele of a mismatch repair gene. In someembodiments, the chemical inhibitor is an anthracene having the formula:

[0033] wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino,alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl,substituted alkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl,N-alkenyl, O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl,aryloxy, substituted aryloxy, heteroaryl, substituted heteroaryl,aralkyloxy, arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl,alkylsulfonyl, alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, analcohol, an amino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehydegroup, an ester, an ether, a crown ether, a ketone, an organosulfurcompound, an organometallic group, a carboxylic acid, an organosiliconor a carbohydrate that optionally contains one or more alkylatedhydroxyl groups; wherein the heteroalkyl, heteroaryl, and substitutedheteroaryl contain at least one heteroatom that is oxygen, sulfur, ametal atom, phosphorus, silicon or nitrogen; and wherein thesubstituents of the substituted alkyl, substituted alkenyl, substitutedalkynyl, substituted aryl, and substituted heteroaryl are halogen, CN,NO₂, lower alkyl, aryl, heteroaryl, aralkyl, aralkoxy, guanidino,alkoxycarbonyl, alkoxy, hydroxy, carboxy and amino; and wherein theamino groups are optionally substituted with an acyl group, or 1 to 3aryl or lower alkyl groups. In certain embodiments, R₅ and R₆ arehydrogen. In other embodiments, R₁-R₁₀ are independently hydrogen,hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl,tolyl, hydroxymethyl, hydroxypropyl, or hydroxybutyl.

[0034] In specific embodiments, the anthracene derivatives include, butare not limited to 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.

[0035] In other embodiments of the method of the invention, the step ofmutagenizing is accomplished using T-DNA insertional mutagenesis.

[0036] The invention also provides polymorphic DNA markers foridentifying herbicide resistant and herbicide susceptible weeds. Thepolymorphic marker comprises a polynucleotide sequence encoding apolypeptide comprising SEQ ID NO: 17. In some embodiments, thepolymorphic DNA marker comprises the polynucleotide sequence of SEQ IDNO: 16 or SEQ ID NO: 126. In other embodiments, the polymorphic markercomprises a sequence encoding a polypeptide that is at least 75%, 80%,85%, 90%, 95%, or 99% identical to SEQ ID NO: 17. In some embodiments,the homolog has the sequence of SEQ ID NO: 60. In other embodiments, thehomolog has a sequence of SEQ ID NO: 61. In other embodiments, thehomologs have the sequences of SEQ ID NO: 127, or SEQ ID NO: 128. Thehomologs have nucleic acid sequences that are at least 80% identical tothat of SEQ ID NO: 126. Preferably, the nucleic acid sequence is atleast 85-90% identical to that of SEQ ID NO: 126. More preferably, thenucleic acid sequence is at least 90-95% identical to that of SEQ ID NO:126. Even more preferably, the nucleic acid sequence is at least 95-99%identical to that of SEQ ID NO: 126.

[0037] The invention also provides a kit for the identification ofherbicide resistant and herbicide susceptible weeds comprising, in oneor more containers, an oligonucleotide primer comprising the sequence ofSEQ ID NO: 18, and a second oligonucleotide primer comprising thesequence of SEQ ID NO: 19. In some embodiments, the kit may furthercomprise a DNA polymerase, deoxynucleotide triphosphates, genomic DNAfrom an herbicide susceptible plant, genomic DNA from an herbicideresistant plant, and/or a DNA polymerase buffer.

BRIEF DESCRIPTION OF DRAWINGS

[0038]FIG. 1 shows a genetic analysis of Glycine max (soybean) cultivarsusing the MOR-1117 marker. PCR analysis of DNA from Am (A1), Wi81 (B1),and CL(C1) cultivars using allele-specific primers demonstrates theability to distinguish cultivars at the genetic level. PCR analysis ofDNA from other plants such as Arabidopsis did not result in a DNAproduct demonstrating the specificity of this assay (not shown). Arrowsindicate products of expected molecular size.

[0039]FIG. 2 shows a gel analysis of PCR-amplified fragments (A) shows afluorescence histogram of HR DNA, (B) is a fluorescence histogram for HSDNA. A 140 bp fragment was identified to be present only in HR butabsent in HS horseweed genomic DNA (arrow).

[0040]FIG. 3 shows a Southern blot using a cloned polymorphic fragmentof Conyza canadensis as a probe for HS and HS weed DNA. Lane 1 and 3 areamplified products from HS, while lane 2 and 4 are those from HR. Lane 5is the insert from the clone. Lanes 1 and 2 are amplified withdye-labeled 2-TG primer while lanes 3 and 4 are amplified with unlabeled2-TG.

[0041]FIG. 4 shows a typical PCR amplification for the MOR9 marker in HSand HR horseweed.

[0042]FIG. 5 shows amplification of MOR9 Homolog 1 (MOR9 H1) fromgenomic DNA of glyphosate resistant (lane 1) and glyphosate susceptible(lane 2) horseweed. Lane 3 shows an amplification reaction in which noDNA was added.

[0043]FIG. 6 shows amplification of MOR9 Homolog 2 (MOR9 H2) fromgenomic DNA of glyphosate resistant (lane 1) and glyphosate susceptible(lane 2) horseweed. Lane 3 shows an amplification reaction in which noDNA was added.

[0044]FIG. 7 shows amplification of SSR markers HGA1, HGA2 and HGA3 fromdifferent biotypes of horseweed (Lane 1: glyphosate susceptible; Lanes2-4: glyphosate resistant; and Lane 5: no DNA added). Each marker wasamplified with two different pairs of primers: Panel (A) shows threegroups of amplifications. The first group shows the results ofamplification using NP1-HGA2 and D-HGA2; the second group shows theresults of amplification using NP2-HGA2 and D-HGA2; the third groupshows the results of amplification using NP1-HGA3 and D-HGA3. Panel (B)shows three groups of amplifications. The first group shows the resultsof amplification using NP2-HGA3 and D-HGA3; the second group shows theresults of amplification using NP1-HGA1 and D-HGA1; the third groupshows the results of amplification using NP2-HGA1 and D-HGA1.

DETAILED DESCRIPTION OF THE INVENTION

[0045] The referenced patents, patent applications, and scientificliterature, including accession numbers to GenBank database sequences,referred to herein are hereby incorporated by reference in theirentirety. Any conflict between any reference cited herein and thespecific teachings of this specification shall be resolved in favor ofthe latter. Likewise, any conflict between an art-understood definitionof a word or phrase and a definition of the word or phrase asspecifically taught in this specification shall be resolved in favor ofthe latter.

[0046] Standard reference works setting forth the general principles ofrecombinant DNA technology known to those of skill in the art include,but are not limited to Ausubel et al. CURRENT PROTOCOLS IN MOLECULARBIOLOGY, John Wiley & Sons, New York (1998); Sambrook et al. MOLECULARCLONING: A LABORATORY MANUAL, 2D ED., Cold Spring Harbor LaboratoryPress, Plainview, N.Y. (1989); Kaufman et al., Eds., HANDBOOK OFMOLECULAR AND CELLULAR METHODS IN BIOLOGY AND MEDICINE, CRC Press, BocaRaton (1995); McPherson, Ed., DIRECTED MUTAGENESIS: A PRACTICALAPPROACH, IRL Press, Oxford (1991).

[0047] As used herein, “breeding” refers to the art and science ofimproving a species of plant or animal through controlled geneticmanipulation.

[0048] As used herein “trait” refers to an observable characteristic ofan organism.

[0049] As used herein “trait allele” refers to a gene with a definedcontribution to an observed characteristic.

[0050] As used herein “trait locus” refers to a genetically definedlocation for a collection of one or more genes (alleles) whichcontribute to an observed characteristic.

[0051] As used herein “weed” refers to undesired vegetation such as thatcan infiltrate commercial crops and domestic plantings. Non-limitingexamples of such undesirable vegetation includes, but is not limited toblack mustard (Brassica nigra), curly dock (Rumex crispus), commongroundsel (Senecio vulgaris), pineapple weed (Matricariamatricarioides), swamp smartweed (kelp) (Polygonum coccineum), pricklylettuce (Lactuca scariola), lance-leaved groundcherry (Physalislanceifolia), annual sowthistle (Sonchus oleraceus), London rocket(Sisymbrium irio), common fiddleneck (Amsinckia intermedia), hairynightshade (Solanum sarrachoides), shepherd's purse (Capsellabursa-pastoris), common knotweed (Polygonum aviculare), green amaranth(Amaranthus hybridus), horseweed (Conyza canadensis), henbit (Lamiumamplexicaule), cocklebur (Xanthium strumarium), cheeseweed (Malvaparviflora), lambsquarters (Chenopodium album), puncture vine (Tribulusterrestris), common purslane (Portulaca oleracea), prostrate spurge(Euphorbia supina), telegraph plant (Heterotheca grandiflora),carpetweed (Mollugo verticillate), yellow starthistle (Centaureasolstitialis), milk thistle (Silybum marianum), mayweed (Anthemiscotula), burning nettle (Urtica urens), fathen (Atriplex patula),chickweed (Stellaria media), scarlet pimpernel (Anagallis arvensis),redroot pigweed (Amaranthus retroflexus), minners-lettuce (Montiaperfoliata), turkey mullein (Eremocarpus setigerus), nettleleafgoosefoot (Chenopodium murale), prostrate pigweed (Amaranthusblitoides), silverleaf nightshade (Solanum elaeagnifolium), hoary cress(Cardaria draba), largeseed dodder (Cuscuta indecora), Californiaburclover (Medicago polymorpha), horse purslane (Trianthemaportulacastrum), field bindweed (Convolvulus arvensis), Russian knapweed(Centaurea repens), flax-leaved fleabane (Conyza bonariensis), wildradish (Raphanus sativus), tumble pigweed (Amaranthus albus),stephanomeria (Stephanomeria exigua), wild turnip (Brassica campestris),buffalo goard (Cucurbita foetidissima), common mullein (Verbascumthapsus), dandelion (Taraxacum officinale), Spanish thistle (Xanthiumspinosum), chicory (Cichorium intybus), sweet anise (Foeniculumvulgare), annual yellow sweetclover (Melilotus indical), poison hemlock(Conium maculatum), broadleaf filaree (Erodium botrys), whitestemfilaree (Erodium moschatum), redstem filaree (Erodium cicutarium),ivyleaf morning-glory (Ipomea hederacea), shortpod mustard (Brassicageniculata), buckhorn plantain (Plantago lacenolata), sticky chickweed(Cerastium viscosum), himalaya blackberry (Rubus procerus), purslanespeedwell (Veronica peregrina), mexicantea (Chenopodium ambrosioides),Spanish clover (Lotus purshianus), Australian brassbuttons (Cotulaaustralia), goldenrod (Solidago californica), citron (Citrulluslanatus), hedge mustard (Sisymbrium orientale), black nightshade(Solanum nodiflorum), chinese thornapple (Datura ferox), bristlyoxtongue (Picris echioides), bull thistle (Cirsium vulgare), spinysowthistle (Sonchus asper), tasmanian goosefoot (Chenopodium pumilio),goosefoot (Chenopodium botrys), wright groundcherry (Physalisacutifolia), tomatillo groundcherry (Physalis philadelphica), prettyspurge (Euphorbia peplus), bitter apple (Cucumis myriocarpus), Indiantobacco (Nicotiana bigelovii), common morning-glory (Ipomoea purpurea),waterplantain (Alisma triviale), smartweed (Polygonum lapathifolium),mature sowthistle (Sonchus asper), yellow nutsedge (Cyperus esculentus),purple nutsedge (Cyperus rotundus), lupine (Lupinus formosus), andgrasses of the family Gramineae such as annual rye grass (Lolium spp.),blue grass, water grass, barnyard grass, Bermuda grass, fescue, matgrass, Johnson grass, and the like. The methods of the invention may beused for any of the weeds listed above or any subset thereof.

[0052] As used herein “crop species” refers to a plant species which iscultivated by man in order to produce a harvestable product.Non-limiting examples of crop species include soybean, corn, sunflower,rapeseed, wheat, barley, oat, rice and sorghum, tomato, potato,cucumber, onion, carrot, common bean, pepper, and lettuce.

[0053] As used herein “phenotypic data” refers to a set of traitobservations made from one or more individuals.

[0054] As used herein “genetic marker” refers to any morphological,biochemical, or nucleic acid-based phenotypic difference which reveals aDNA polymorphism. Examples of genetic markers include, but are notlimited to, RFLPs, RAPDs, AFLPs, allozymes and SSRs.

[0055] As used herein “genetic marker locus” refers to a geneticallydefined location for a collection of one or more DNA polymorphismsrevealed by a morphological, biochemical or nucleic acid-bred analysis.

[0056] As used herein “genetic marker allele” refers to an observedclass of DNA polymorphism at a genetic marker locus. For most types ofgenetic markers (RFLPS, allozymes, SSRs, AFLPs, RADs), alleles areclassified based upon DNA fragment size. Individuals with the sameobserved fragment size at a marker locus have the same genetic markerallele and thus are of the same allelic class.

[0057] “Genomic analysis” as used herein, can involve any of a varietyof methods used by those skilled in the art for identifying linked genesby genetic mapping, as well as methods to detect gene mutations and/ordifferential gene expression, including but not limited to differentialgene expression using microarrays, cDNA subtraction, differentialprotein analysis, complementation assays, single nucleotide polymorphism(SNP) analysis or whole genome sequencing to identify altered loci.

[0058] “Herbicides” as used herein refers to compounds that kill orretard the growth of plant tissue. Examples of herbicides include, butare not limited to glyphosate, paraquot, sulfonyl urea moities,aminoglycosides, 5-enolpyruvylshikimate-3-phosphate synthase inhibitors,triazine-based herbicides, beta-lactams, macrolides, lincosamides,sulfonamides, Atrazine, Alachlor, isoniazids, and metribuzin.

[0059] As used herein “genotyping” refers to the process of determiningthe genetic composition of individuals using genetic markers.

[0060] As used herein “genotype” refers to the allelic composition of anindividual at genetic marker loci under study.

[0061] As used herein “breeding population” refers to a geneticallyheterogeneous collection of plants created for the purpose ofidentifying one or more individuals with desired phenotypiccharacteristics.

[0062] As used herein, “T-DNA” refers to the DNA sequence, a copy ofwhich gets transferred from Agrobacterium to the plant cell.

[0063] As used herein, “T-DNA borders” refers to the DNA sequences thatflank the T-DNA.

[0064] The term “transforming” or “transformation” refers to the processof introducing DNA into a recipient cell. In some embodiments of theinvention, transformation refers to introducing DNA into a recipientplant cell and its subsequent integration into the plant cell'schromosomal DNA. The process of transfection can be carried out in aliving plant, or it can be carried out in vitro, e.g., using asuspension of one or more isolated cells in culture. In general,transfection will be carried out using a suspension of cells, or asingle cell, but other methods can also be applied as long as asufficient fraction of the treated cells or tissue incorporates thepolynucleotide so as to allow transfected cells to be grown andutilized. The protein product of the polynucleotide may be transientlyor stably expressed in the cell. Techniques for transfection are wellknown. Available techniques for introducing polynucleotides include butare not limited to electroporation, Agrobacterium-mediatedtransformation, T-DNA-mediated transformation, and particle bombardment.Once a cell has been transfected with the mismatch repair gene, the cellcan be grown and reproduced in culture. If the transfection is stable,such that the gene is expressed at a consistent level for many cellgenerations, then a cell line results. In some embodiments, the DNAcomes from a large plasmid in the Agrobacterium known as the Ti (Tumorinduction) plasmid. The Ti-plasmid comprises several vir (virulence)genes, whose products are directly involved in T-DNA processing andtransfer. Located within the natural T-DNA are genes for plant growthregulators and amino acid derivatives, which are for the sole benefit ofthe Agrobacterium, but are not necessary for the transfer of the T-DNAand its integration into the plant genome. Natural Ti-plasmids are verylarge. To make it useful for the purpose of plant transformations, twochanges may be made to the Ti-plasmids:

[0065] 1. All the genes within the T-DNA may be removed and replacedwith any DNA sequence that one wants to transfer to the plant cell, suchas a dominant negative mismatch repair gene.

[0066] 2. The T-DNA itself is removed from the Ti-plasmid and is placedon a novel plasmid called the “binary vector.”

[0067] Together with the Ti-plasmid, this binary vector co-exists andreplicates within Agrobacterium. The binary vector is relatively smallit is relatively easy to work with. A copy of a short region of DNA(i.e., the T-DNA) in the binary vector is transferred to the plant cell,where it becomes stably integrated into the plant genome, i.e., theplant cell's chromosomal DNA. The construction of binary vectorscontaining T-DNAs capable of being inserted into a plant genome viaAgrobacterium mediated delivery is known to those skilled in the art. Inaddition to the DNA sequence of interest, a selectable marker gene canbe placed within the T-DNA borders in order to allow selection forplants transformed with the DNA sequence of interest. Such selectablemarker genes include aph4, for hygromycin resistance, npt2, forkanamycin resistance, bar for Basta resistance, cp4 for glyphosateresistance. Further information of T-DNA transformation of plant cellsmay be found in U.S. Pat. No. 6,353,155, the disclosure of which isincorporated herein by reference.

[0068] The invention provides methods for identifying polymorphic DNAmarkers in naturally occurring HR weeds to identify haplotypes ofbiotypes that are resistant to herbicides for the early diagnosis of HRweeds at the vegetative stage as a method for helping farmers adjust andimplement proper crop management strategies.

[0069] In the method of the invention, polymorphic markers of herbicideresistance in a plant are identified by: (a) isolating genomic DNA froman herbicide susceptible plant and an herbicide resistant plant;(b)performing genetic analysis on said genomic DNA of said an herbicidesusceptible plant and said herbicide resistant plant; and (c)identifying differences between the genomic DNA of said herbicidesusceptible plant and said herbicide resistant plant, therebyidentifying polymorphic markers of herbicide resistance in said plant.

[0070] In some embodiments of the invention, field isolates of weedsthat are resistant to a selected class of compound or compounds areisolated and their nucleic acid is extracted. The same is done forsubtypes of the weeds that are HS. DNA markers are identified and can beanalyzed using a variety of methods for identifying altered nucleotidestructures including genotyping of repetitive sequences usingmicrosatellite markers to identify linked genomic segments that areassociated with a particular trait, single nucleotide polymorphic (SNP)analysis using a variety methods known to those skilled in the art, aswell as standard Restriction Fragment Length Polymorphism (RFLP)(Botstein et al. (1980) Am. J. Hum. Genet. 32:314-331) and AmplifiedFragment Length Polymorphism (AFLP) methods (Vos et al., (1995) Nucl.Acids Res. 23:4407-4414). It is understood that mutant genes could alsobe identified by other types of genetic markers such as, for example,Simple Sequence Length Polymorphisms (SSLPs) (Tautz and Renz (1984)“Simple sequences are ubiquitous repetitive components of eukaryoticgenomes” Nucl. Acids Res. 25:12(10):4127-38), Randomly AmplifiedPolymorphic DNAs (RAPDs) (Williams et al. (1990) “OligonucleotidePrimers of Arbitrary Sequence Amplify DNA Polymorphisms which are Usefulas Genetic Markers” Nucleic Acids Res. 18:6531-6535), DNA AmplificationFingerprinting (DAF) (Caetano-Anolles et al. (1991) Biotechnol.9(6):553-557), Sequence Characterized Amplified Regions (SCARs) (Paranand Michelmore (1993) Theor. Appl. Genet. 85:985-993), Arbitrary PrimedPolymerase Chain Reaction (AP-PCR) (Welsh and McClelland (1990) NucleicAcids Res. 18:7213-7218), Amplified Fragment Length Polymorphisms(AFLPs) and Single Nucleotide Polymorphisms (SNPs) (Wang et al. (1998)“Large-Scale Identification, Mapping, and Genotyping ofSingle-Nucleotide Polymorphisms in the Human Genome” Science280:1077-1082). In particular, in some embodiments identification ofpolymorphic markers for glyphosate resistant plants such as Conyzacanadensis, and members of the rigid ryegrass and goosegrass familiesare identified.

[0071] In some embodiments, the polymorphic markers comprisepolynucleotide microsatellite markers where herbicide resistant plantshave a distinct haplotype pattern in comparison to herbicide susceptiblespecies. In one non-limiting embodiment, polymorphic markers areidentified by isolating genomic DNA from glyphosate resistant andsusceptible field-isolate weeds, identifying polymorphic DNA sequencescontaining single nucleotide polymorphisms, polynucleotide tractscomprising of mono-, di-, tri- or tetra-repetitive units, identifyingflanking sequences and designing primers that are specific for eachlocus for analysis using methods as known by those skilled in the art.

[0072] The invention also provides methods for identifying genesinvolved in herbicide resistance and susceptibility comprising: (a)isolating genomic DNA from and herbicide susceptible plant and anherbicide resistant plant of the same species; (b) performing geneticanalysis on the genomic DNA of the herbicide susceptible plant and anherbicide resistant plant; (c) identify genetic differences between thegenomic DNA of the herbicide susceptible plant and an herbicideresistant plant; and (d) sequence the DNA in the regions comprising thegenetic differences. Thus, one can identify the genes associated withherbicide susceptibility and resistance in the plants. The geneticanalysis may be by any means known in the art and as described herein.

[0073] In some embodiments, DNA fragments derived from an herbicidesusceptible plant may be isolated and introduced into an herbicideresistant plant. The herbicide resistant plant then contains DNAfragments with altered sequences that are responsible for the herbicidesusceptible phenotype. The recombinant plants may then be screened forherbicide susceptibility and the DNA fragments introduced into theplants may be sequenced to identify the gene candidates responsible forthe herbicide susceptible phenotype. Conversely, in other embodiments,DNA fragments derived from an herbicide resistant plant may be isolatedand introduced into an herbicide susceptible plant. The herbicidesusceptible plant then contains DNA fragments with altered sequencesthat are responsible for the herbicide resistant phenotype. Therecombinant plants may then be screened for herbicide resistance and theDNA fragments introduced into the plants may be sequenced to identifythe gene candidates responsible for the herbicide resistance phenotype.

[0074] In another embodiment of the invention, genetic analysis iscoupled with traditional plant breeding and crossing to provide a methodfor identifying genes involved in susceptibility and resistance toherbicides. For example, the invention provides a method in which anherbicide resistant strain is crossed with an herbicide susceptiblestrain and the progeny are screened for herbicide resistance. Progenythat are resistant can be subjected to genetic analysis and comparedwith genetic analysis of the susceptible strain to determine the geneticdifferences between the strains. The genes may then be sequenced andidentified. Optionally, progeny that are found to be herbicide resistantmay be back-crossed one or more times with herbicide susceptible strainsand the subsequent progeny re-screened for herbicide resistance. Thesubsequent progeny should have fewer genetic differences, reducing thenumber of genes to be identified. In another embodiment, progeny thatare found to be herbicide susceptible may be back-crossed one or moretimes with herbicide resistant strains and the subsequent progenyre-screened for herbicide susceptibility. Again, backcrossing more thanonce should reduce the number of genetic differences between the strainsand reduce the number of genes to be identified and sequenced. Themethods for genetic analysis may be any known in the art and asdescribed herein.

[0075] Methods for the diagnosis of HR weeds are provided that can beused to screen for weed biotypes to detect HR-weeds at any developmentalstage. The methods are useful to farmers, for example, to make propercrop management decisions prior to planting. The invention providesmethods to identify DNA markers that are linked to genomes of particularresistant weeds. The invention also provides methods to generate a widearray of genomic alterations in an HR weed's genome that can yieldmaximal number altered target genes that are capable of elicitingsusceptibility to a particular herbicide. Using herbicide susceptible(HS) strain developed by the method of the invention, genome analysisidentifies mutant gene(s) that are capable of rendering a plantresistant or susceptible to an herbicide for target identification.Methods of genome analysis are known by those skilled in the art of genemapping and mutation detection.

[0076] The invention also provides methods of using field isolates thatare naturally resistant to an herbicide or class of herbicide, in genemapping studies in conjunction with crossing resistant strains tosusceptible strains.

[0077] In addition, the invention provides methods for generating mutantoffspring from herbicide resistant (HR) weeds to create herbicidesusceptible (HS) types from strains that are naturally resistant toparticular herbicide or class of herbicides are useful for identifyinggenes responsible for HR as diagnostic markers as well as for herbicidecompound screening and development.

[0078] In some embodiments of the methods of the invention, mutationsare introduced in the plant species to generate genetic diversity.Previously, a bottleneck to generating genetically diverse plants wasthe inability to generate nonbiased genome-wide mutations. Manymutagenesis methods used chemical and radiation exposure to generategenomic mutations. A limitation of this approach was that these variousmethods are usually DNA site-specific or are extremely toxic, thereforelimiting the mutation spectra and the opportunity to identify a maximalnumber of genes, when mutated, that are able to confer resistance to anherbicide. Recently, work by Nicolaides, et al. (1998) Mol. Cell. Biol.18(3):1635-1641; U.S. Pat. No. 6,146,894) has demonstrated the utilityof introducing dominant negative mismatch repair (MMR) mutants intocells to confer global DNA hypermutability. These mutations are in theform of point mutations or small insertion-deletions that aredistributed equally throughout the genome. The ability to manipulate theMMR process of a target host organism can lead to an increase in themutability of the target host genome, leading to the generation ofinnovative cell subtypes with varying phenotypes from the original wildtype cells. Variants can be placed under a specified, desired selectiveprocess the result of which is the capacity to select for a novelorganism that expresses an altered biological molecule(s) and has a newphenotype. The concept of creating and introducing dominant negativeallele of a MMR gene in cells has been documented to result ingenetically altered cells (Aronshtam A, and M. G. Marinus (1996)“Dominant negative mutator mutations in the mutL gene of Escherichiacoli” Nucleic Acids Res. 24:2498-2504; Wu, T. H. and M. G. Marinus(1994) “Dominant negative mutator mutations in the mutS gene ofEscherichia coli” J. Bacteriol. 176:5393-400; Brosh R. M. Jr, and S. W.Matson (1995) “Mutations in motif II of Escherichia coli DNA helicase IIrender the enzyme nonfunctional in both mismatch repair and excisionrepair with differential effects on the unwinding reaction” J.Bacteriol. 177:5612-5621; Nicolaides, N. C. et al. (1998) “A naturallyoccurring hPMS2 mutation can confer a dominant negative mutatorphenotype” Mol. Cell. Biol. 18:1635-1641). Furthermore, altered MMRactivity has been demonstrated when MMR genes from different speciesincluding yeast and mammalian cells are over-expressed (Lipkin S. M. etal. (2000) “MLH3: a DNA mismatch repair gene associated with mammalianmicrosatellite instability” Nat. Genet. 24:27-35). The inhibition of MMRin organisms has been documented to generate hypermutation in wholeorganisms (WO 01/61012 (US2002128460); de Wind N. et al. (1995)“Inactivation of the mouse MSH2 gene results in mismatch repairdeficiency, methylation tolerance, hyperrecombination, andpredisposition to cancer” Cell 82:321-300). The ability to createhypermutable organisms by blocking MMR has great commercial value forthe generation of HS plants from naturally HR strains and vice-versa fordiagnosis, drug screening, and target discovery of genes involved inthese phenotypes in addition to the important utility for the earlydiagnosis of weeds to aid farmers in deciding the most appropriate cropmanagement systems for maximal harvest potential.

[0079] The methods of the invention may employ inhibiting mismatchrepair in the weeds by introducing a dominant negative mismatch repairgene into the plant. As used herein, “mismatch repair gene” refers to agene that encodes one of the proteins of the mismatch repair complex.Although not wanting to be bound by any particular theory of mechanismof action, a mismatch repair complex is believed to detect distortionsof the DNA helix resulting from non-complementary pairing of nucleotidebases. The non-complementary base on the newer DNA strand is excised,and the excised base is replaced with the appropriate base which iscomplementary to the older DNA strand. In this way, cells eliminate manymutations that occur as a result of mistakes in DNA replication.Dominant negative alleles cause a mismatch repair defective phenotypeeven in the presence of a wild-type allele in the same cell. Anon-limiting example of a dominant negative allele of a mismatch repairgene is the human gene hPMS2-134, which carries a truncation mutation atcodon 134. The mutation causes the product of this gene to abnormallyterminate at the position of the 134th amino acid, resulting in ashortened polypeptide containing the N-terminal 133 amino acids. Such amutation causes an increase in the rate of mutations which accumulate incells after DNA replication. Thus, expression of a dominant negativeallele of a mismatch repair gene results in impairment of mismatchrepair activity, even in the presence of the wild-type allele.

[0080] The mismatch repair gene may be a dominant negative mismatchrepair gene, including, but not limited to a dominant negative form ofPMS2, PMS1, PMSR3, PMSR6, MLH1, GTBP, MSH3, MSH2, MSH6-1, MSH7, or MSH1.A non-limiting example includes a dominant negative truncation mutant ofPMS2 (e.g., a PMS2-134 gene) (SEQ ID NO: 34).

[0081] Examples of mismatch repair genes sequences and proteins areshown by the following: Yeast MLH1 cDNA (SEQ ID NO: 22); Yeast MLH1protein (SEQ ID NO: 23); Mouse PMS2 cDNA (SEQ ID NO: 24); mouse PMS2protein (SEQ ID NO: 25); human PMS2 cDNA (SEQ ID NO: 26); human PMS2protein (SEQ ID NO: 27); human PMS1 cDNA (SEQ ID NO: 28); human PMS1protein (SEQ ID NO: 29); human MSH2 cDNA (SEQ ID NO: 30); human MSH2protein (SEQ ID NO: 31); human MLH1 cDNA (SEQ ID NO: 32); human MLH1protein (SEQ ID NO: 33); human PMS2-134 cDNA (SEQ ID NO: 34); humanPMS2-134 protein (SEQ ID NO: 35); human MSH6 cDNA (SEQ ID NO: 36); humanMSH6 protein (SEQ ID NO: 37); human PMSR2 cDNA (SEQ ID NO: 38); humanPMSR2 protein (SEQ ID NO: 39); human PMSR3 cDNA (SEQ ID NO: 40); humanPMSR3 protein (SEQ ID NO: 41); human PMSL9 cDNA (SEQ ID NO: 42); humanPMSL9 protein (SEQ ID NO: 43); Arabidopsis thaliana MSH7 cDNA (SEQ IDNO: 44); Arabidopsis thaliana MSH7 protein (SEQ ID NO: 45); Arabidopsisthaliana MSH2 cDNA (SEQ ID NO: 46); Arabidopsis thaliana MSH2 protein(SEQ ID NO: 47); Arabidopsis thaliana MSH3 cDNA (SEQ ID NO: 48);Arabidopsis thaliana MSH3 protein (SEQ ID NO: 49); Arabidopsis thalianaMSH6-1 cDNA (SEQ ID NO: 50); Arabidopsis thaliana MSH6-1 protein (SEQ IDNO: 51); Arabidopsis thaliana PMS2 cDNA (SEQ ID NO: 52); Arabidopsisthaliana PMS2 protein (SEQ ID NO: 53); Arabidopsis thaliana PMS2-134cDNA (SEQ ID) NO: 54); Arabidopsis thaliana PMS2-134 protein (SEQ ID NO:55); Oryza sativa MLH1 cDNA (SEQ ID NO: 56); and Oryza sativa MLH1protein (SEQ ID NO: 67).

[0082] The methods of the invention include the use of chemicalinhibitors or mismatch repair to induce mutations in the weeds toconvert herbicide resistant weeds into herbicide susceptible weeds, orvice versa. The chemical inhibitors of mismatch repair include, but arenot limited to an anthracene, an ATPase inhibitor, a nuclease inhibitor,a polymerase inhibitor and an antisense oligonucleotide thatspecifically hybridizes to a nucleotide encoding a mismatch repairprotein.

[0083] In some embodiments, the chemical inhibitor is an anthracenehaving the formula:

[0084] wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino,alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl,substituted alkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl,N-alkenyl, O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl,aryloxy, substituted aryloxy, heteroaryl, substituted heteroaryl,aralkyloxy, arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl,alkylsulfonyl, alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, analcohol, an amino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehydegroup, an ester, an ether, a crown ether, a ketone, an organosulfurcompound, an organometallic group, a carboxylic acid, an organosiliconor a carbohydrate that optionally contains one or more alkylatedhydroxyl groups; wherein said heteroalkyl, heteroaryl, and substitutedheteroaryl contain at least one heteroatom that is oxygen, sulfur, ametal atom, phosphorus, silicon or nitrogen; and wherein saidsubstituents of said substituted alkyl, substituted alkenyl, substitutedalkynyl, substituted aryl, and substituted heteroaryl are halogen, CN,NO₂, lower alkyl, aryl, heteroaryl, aralkyl, aralkoxy, guanidino,alkoxycarbonyl, alkoxy, hydroxy, carboxy and amino; and wherein saidamino groups are optionally substituted with an acyl group, or 1 to 3aryl or lower alkyl groups. In certain embodiments, R₅ and R₆ arehydrogen. In other embodiments, R₁-R₁₀ are independently hydrogen,hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl,tolyl, hydroxymethyl, hydroxypropyl, or hydroxybutyl.

[0085] Non-limiting examples of the anthracenes include1,2-dimethylanthracene, 9,10-dimethylanthracene, 7,8-dimethylanthracene,9,10-diphenylanthracene, 9,10-dihydroxymethylanthracene,9-hydroxymethyl-10-methylanthracene, dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene. The chemical inhibitors of mismatch repairare more fully described in PCT Publication No. WO 02/054856, which isincorporated by reference in its entirety.

[0086] In the method of the invention, polymorphic DNA markers may beidentified by genotyping an herbicide resistant plant and an herbicidesusceptible plant of the same species. The HR and HS plants may benatural field isolates, modified genetically as described in the methodsabove, or may have been generated using traditional breeding andselection. The genotyping may be performed using any form of genotypingknown in the art, as described above.

[0087] In other embodiments of the method of the invention, diversity isgenerated in the plants by introducing T-DNA into the genome of anherbicide resistant or herbicide susceptible strain. The T-DNA may beused to introduce a dominant negative allele of a mismatch repair geneinto the plant.

[0088] Methods for transforming dicotyledenous species withAgrobacterium are well established in the art. Recently, it has beenshown that monocotyledenous plants may also be transformed using A.tumefaciens transformation methods. It has been shown that the followingmonocots could be transformed using Agrobacterium transformation: corn(Zea mays L.); wheat (Triticum aestivum L.); rice (Oryza sativa L.);barley (Hordeum vulgare L.); sugar cane (Saccharum spp. L.); (Anthuriumscherzerianum Schott ‘Rudolph’ and ‘UH1060’); orchid (Phalaenopsisspp.); and iris (Iris germamica L. ‘Skating Party’) (See Arencibia etal. (1998) Transgenic Res. 7:213-222; Cheng et al. (1997) Plant Physiol.115:971-980; Hiei et al. (1994) Plant J. 6:271-282; Ishida et al. (1996)Nature Biotechnol. 14:745-750; Tingay et al. (1997) Plant J.11:1369-1375; Chen and Kuehnle (1996) J. Amer. Soc. Hort. Sci.121:47-51; Belarmino and Mii (2000) Plant Cell Rpt. 19:435-442; and U.S.Pat. No. 6,459,017).

[0089] The invention provides methods for identifying herbicideresistant (HR) forms of weeds to help farmers apply appropriate cropmanagement systems. The ability to identify genome haplotypes in weedsthat can determine herbicide resistant (HR) biotypes from herbicidesusceptible (HS) biotypes will aid in the rapid analysis of weeds priorto planting and allow for the appropriate design of crop managementsystems for farmers. For example, with knowledge of the type ofherbicide resistance prevalent in the weed population, farmers maychoose more appropriate herbicides to control the growth of weeds amongtheir crops.

[0090] The invention also provides methods for developing mutantoffspring from naturally occurring HR weeds by mutagenesis methodsincluding but not limited to chemical mutagenesis, radiationmutagenesis, or by altering the activity of endogenous mismatch repair(MMR) activity of hosts to generate HS offspring for target discovery.In addition, HS plants are useful for screening chemical libraries toidentify novel herbicide agents as well as for the rational design ofchemicals for herbicide product development. Mutagens affecting mismatchrepair and dominant negative alleles of mismatch repair genes, whenapplied to plants, are examples of how to mutagenize weeds by increasingthe rate of spontaneous mutations through the reduction of MMR-mediatedDNA repair activity, thereby rendering plants highly susceptible togenetic alterations due to hypermutability. Hypermutable weeds can beutilized to screen for novel mutations in a gene or a set of genes thatproduce variant siblings exhibiting new output traits not found in thewild type plants such as HS in plants whereby the parental strain isnaturally HR.

[0091] The invention also provides a method for screening for HR and HSConyza canadensis. The method is a PCR-based assay in which plantgenomic DNA is amplified with primers that specifically amplify aportion of plant DNA present in HR Conyza canadensis, but not HS Conyzacanadensis. The primers used in the assay are PCR Primer 1: 5′-TTG TCGCTG TCC AAC CAT TG-3′ SEQ ID NO: 18); PCR Primer 2: 5′-TTG GCA TGG TCTGTA GCT GG-3′ SEQ ID NO: 19); Control PCR Primer 1: 5′-CCA TCG TAT CATCAT GTG C-3′ SEQ ID NO: 20); and Control PCR Primer 2: 5′-TGC AAT ATGTTA AAG TAG AGC-3′ SEQ ID NO: 21). PCR Primer 1 (SEQ ID NO: 18) and PCRPrimer 2 (SEQ ID NO: 19) specifically amplify a portion of genomic DNAfrom HR Conyza canadensis, but do not amplify any product from HS Conyzacanadensis. Control PCR Primer 1 (SEQ ID NO: 20) and Control PCR Primer2 (SEQ ID NO: 21) may be used to amplify a product from both HR and HSConyza canadensis. The conditions of the PCR are not particularlylimited, and may be performed following any of the many protocols andvariations known in the art. The primers used in the method of theinvention may have alterations at the 5′ end to engineer restrictionsites, and may have substituted nucleotides throughout the primerprovided the oligonucleotide sequence is at least 80% identical to theprimers shown for SEQ ID NOs: 18, 19, 20 and 21, and comprise theidentical three 3′ nucleotides for each primer.

[0092] The method also provides polymorphic markers of Conyza canadensiswhich may be used to distinguish herbicide resistant or herbicidesusceptible plants. The polymorphic markers comprise MOR9 (SEQ ID NO: 16and SEQ ID NO: 126), as well as homologs MOR9 H1 (SEQ ID NO: 60 and SEQID NO: 127), and MOR9 H2 (SEQ ID NO: 61 and SEQ ID NO: 128). Thepolymorphic markers further comprise the nucleotide sequences of SEQ IDNO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86,SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO:91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ IDNO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO:105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQID NO: 110, and SEQ ID NO: 111

[0093] The invention also provides a kit for screening for HS and HRConyza canadensis comprising in one or more containers, a set of primersfor amplifying a portion of DNA from HR Conyza canadensis. In someembodiments, the kit further comprises other components, such as, butnot limited to, a DNA polymerase, dNTPs, control primers, control DNA,DNA polymerase buffer, and instructions for use. In some embodiments,the primers for amplifying a portion of DNA from HR Conyza canadensis,comprise oligonucleotide primers having the sequences of SEQ ID NO: 18and SEQ ID NO: 19. In some embodiments, the control PCR primers compriseoligonucleotide primers comprising the sequences of SEQ ID NO: 20 andSEQ ID NO: 21.

[0094] In general, the oligonucleotide primers that may be used toamplify a polymorphic marker of herbicide resistant plants is at least15 nucleotides in length and at least 85% identical to a portion of apolymorphic marker selected from the group consisting of SEQ ID NO: 16,SEQ ID NO: 126, SEQ ID NO: 60, SEQ ID NO: 127, SEQ ID NO: 61, SEQ ID NO:128, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ IDNO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90,SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO:95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104,SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ IDNO: 109, SEQ ID NO: 110, and SEQ ID NO: 111. The oligonucleotide primersof the invention anneal to a complementary portion of the polymorphicmarkers under PCR conditions, which are well-known in the art. In someembodiments, the oligonucleotide has a 3′ end that comprises at least 3identical nucleotides of a portion of at least one of the abovepolymorphic markers in addition to the other stated characteristics ofthe oligonucleotide primer.

[0095] The invention also provides a genetic marker for HR Conzyacanadensis, MOR9, comprising SEQ ID NO: 16. The MOR9 marker comprises anopen reading frame comprising the amino acid sequence of SEQ ID NO: 17.The invention comprises a genetic marker having the open reading frameencoding SEQ ID NO: 17, and homologs thereof. As used herein, “homolog”refers to a sequence from Conzya canadensis, other Conzya spp., oranother type and species of weed having an amino acid sequence that isat least 70-75% identical to the MOR9 marker having the amino acidsequence of SEQ ID NO: 17. Preferably, the homolog will have a sequencethat is at least 75-85% identical to the amino acid sequence of SEQ IDNO: 17. More preferably, the homolog will have a sequence that is atleast 85-90% identical to the amino acid sequence of SEQ ID NO: 17. Evenmore preferably, the homolog will have a sequence that is at least90-95% identical to the amino acid sequence of SEQ ID NO: 17. Even morepreferably, the homolog will have a sequence that is at least 95-99%identical to the amino acid sequence of SEQ ID NO: 17.

[0096] Kits of the invention for amplifying at least a portion of apolymorphic marker of herbicide resistance comprise in one or morecontainers at least one oligonucleotide primer of the invention thatanneals to a polymorphic marker of the invention under PCR conditions.

[0097] The invention also provides methods to screen for new forms ofherbicide agents that are active against genes, their correspondingproducts and pathways by employing structural information of the genes,the gene products and mutant strains. Positive compounds can then beused as final products or precursors to be further developed intoherbicidal agents.

[0098] In a further embodiment of the invention, a profile of theisolated markers of the invention are used to as diagnostic tools toidentify haplotypes from field isolates of weeds that are associatedwith HR or HS. DNA is isolated from HR and HS biotypes, and polymorphicmarkers are isolated in accordance with the methods of the invention.Markers are analyzed for nucleotide structure to identify markersassociated with HR or HS. The markers are used to screen field-isolatesto HR and HS weeds. Crop management regarding appropriate herbicides isimproved by identifying the resistance states of field isolates.

[0099] In another embodiment of the invention, a method is provided forscreening weeds using polymorphic markers to identify HR and HSbiotypes.

[0100] In another embodiment of the methods of the invention, plants areexposed to at least one chemical mutagen and seeds are grown in thepresence of the herbicide of interest to identify parental plants thathave been mutated in a gene(s) or pathways involved in herbicideresistance. Mutant offspring are subject to genormic analysis genes areisolated to serve as diagnostic markers and/or therapeutic agentdevelopment.

[0101] In an embodiment of the therapeutic agent development, genesinvolved with herbicide resistance or susceptibility may be used toscreen for agents that modify the expression of the gene or its proteinproduct to effect a change in herbicide resistance. For example, but notby way of limitation, a gene conferring herbicide resistance may betargeted with an antisense molecule to decrease the expression of theprotein product and thereby interfere with herbicide resistance. Inanother non-limiting example, the gene conferring herbicidesusceptibility may be inserted into an expression vector and expressedin a recombinant cells system. Isolated or purified protein may becontacted with a panel of compounds to determine which compounds bind tothe protein. Agents that bind to the protein may be further screened forthe ability to interfere with herbicide susceptibility. Such agents maybe, but are not limited to small molecules and proteins. Therapeuticsmay be administered to crop plants to increase their resistance toherbicides while untreated weeds will remain susceptible, for example.

[0102] Although several methods of mutagenesis can generate mutantplants, the invention provides methods for generating HS offspring fromHR plants. The agents to induce mutagenesis include inhibitors ofmismatch repair (MMR), which can lead to as much as a 1000-fold increasein the endogenous DNA mutation rate of a host; the use of chemicalagents and their respective analogues such as ethidium bromide, EMS,MNNG, MNU, tamoxifen, 8-hydroxyguanine, as well as others including butnot limited to those described in: Khromov-Borisov, N. N., et al.(Mutat. Res. 430:55-74, 1999); Ohe, T., et al. (Mutat. Res. 429:189-199,1999); Hour, T. C. et al. (1999) Food Chem. Toxicol. 37:569-579; Hrelia,P., et al. (1999) Chem. Biol. Interact. 118:99-111; Garganta, F., et al.(1999) Environ. Mol. Mutagen. 33:75-85; Ukawa-Ishikawa S., et al. (1998)Mutat. Res. 412:99-107); www.ehs.utah.edu/ohh/mutagens. Such agents canbe used to further enhance the spectrum of mutations and increase thelikelihood of obtaining alterations in one or more genes that can inturn generate naturally occurring HS host weeds from UR parentalstrains. MMR deficiency leads to hosts with an increased resistance totoxicity by chemicals with DNA damaging activity. Thus, additionalgenetically diverse hosts can be generated in embodiments of theinvention wherein MMR defective plants are exposed to such agents.Generation of such genetically diverse hosts would be otherwiseimpossible, due to the toxic effects of such chemical mutagens (Colella,G., et al.(1999) Br. J. Cancer 80:338-343; Moreland, N.J., et al. (1999)Cancer Res. 59:2102-2106; Humbert, O., et al. (1999) Carcinogenesis20:205-214; Glaab, W. E., et al. (1998) Mutat. Res. 398:197-207).Moreover, MMR is responsible for repairing chemical-induced DNA adducts.Therefore, blocking this process would increase the number, types, andrate of mutation and genomic alterations of a weed host (Rasmussen, L.J. et al. (1996) Carcinogenesis 17:2085-2088; Sledziewska-Gojska, E., etal. (1997) Mutat. Res. 383:31-37; and Janion, C. et al. (1989) Mutat.Res. 210:15-22). In addition to the chemicals listed above, other typesof DNA mutagens include ionizing radiation and UV-irradiation, which areknown to cause DNA mutagenesis can also be used to potentially enhancethis process alone or in combination with MMR deficiency.

[0103] The HS weed strains described herein have either been generatedand characterized in a manner which essentially provides a process bywhich the manipulation of host genomic DNA of the MR parental line canconfer susceptibility against a range of compounds and that thesestrains are now useful for target discovery and/or therapeutic agentdiscovery as screening lines.

[0104] The above disclosure generally describes the present invention. Amore complete understanding can be obtained by reference to thefollowing specific examples that will be provided herein for purposes ofillustration only, and are not intended to limit the scope of theinvention.

EXAMPLES Example 1

[0105] Isolation of DNA Markers for Haplotype Analysis of Weeds forGenomic Identification of Herbicide Resistant Biotypes.

[0106] Polymorphic DNA markers are important for mapping the location ofgenes involved in the biochemical pathway of a given phenotype.Polymorphic markers are useful for the unequivocal identification ofweeds that are part of a heterogeneous family that are resistant andsusceptible to certain types of herbicides. These markers can be usedfor the rapid diagnosis of subtypes that are herbicide resistant tocertain classes of chemicals to guide farmers on choosing appropriateherbicide management systems for crop management. One such example forusing DNA markers to identify HR plants is the isolation of genomic DNAfrom field specimens of the Conyza canadensis species whereapproximately 15% of the field populations are naturally resistant toglyphosate, the active ingredient in Roundup® herbicide (VanGessel, M.(2000) “Group G/9 Resistant Horseweed (Conyza canadensis) USA: Delaware”www.weedscience.org/USA.; Robert, S. and U. Baumann (1999) “Resistanceto the herbicide glyphosate” Nature 395:25-26; Mountain, W. (1992)Horseweed, Conyza canadensis (L.) Cronq. Regulatory Horticulture, PADept. of Agriculture 18(1):31-35). Genomic DNA is isolated from HR andHS Conyza canadensis using DNazol method as described by themanufacturer (Gibco/BRL). Polymorphic markers such as, but not limitedto microsatellites, SNPs, and RFLPs can be isolated and used as reagentsto identify biotypes of a particular resistance or susceptibility to aclass of herbicide.

[0107] One approach involves the generation of genomic libraries usingEcoRI fragments from genomic DNA of the host, which are then subclonedinto Lambda Zap cloning vectors and screened for polyA or polyCAnucleotide repeat markers using radiolabelled probes that can identifyrecombinant clones containing specific repeat markers as previouslydescribed (Leach, F. S. et al. (1993) “Mutations of a mutS homolog inhereditary noncolorectal cancer” Cell 75:1215). Positive clones are thenisolated and sequenced to identify the nucleotide-specific sequencescontained within the flanking regions of the repeat marker. Next,oligonucleotide primers are designed and synthesized for gene-specificidentification using the polymerase chain reaction (PCR) as described(Nicolaides, N. C. et al. (1995) “Genomic organization of the human PMS2gene family” Genomics 30:195). Reactions are carried out using 1 ng ofplant DNA as template and the appropriate corresponding primers in 25 ulreactions containing 67 mM Tris, pH 8.8, 16.6 mM (NH₄)₂SO, 6.7 mM MgCl₂,10 mM 2-mercaptoethanol, 4% DMSO, 1.25 mM each of the four dNTPs, 175 ngof each cDNA specific primer and 1U of Taq polymerase at 94° C. for 30seconds, 54° C. for 30 seconds and 72° C. for 30 seconds for 30 cycles.Reactions are then added to loading buffer containing 0.05% bromophenolblue plus 10% glycerol and loaded onto 5% METAPHOR agarose gels. Gelsare electrophoresed at 150V for 3 hours at 4° C. in tris-acetate runningbuffer, stained with ethidium bromide and DNA products are visualized byultraviolet light using a transilluminator. A typical example and resultof this procedure is shown in FIG. 1 whereby a novel marker for Glycinemax (MOR-117) was isolated using the methods described above from twoclosely related species that exhibit distinct phenotypes. Markerspecific primers were optimized for PCR and genome analysis of threedifferent soybean cultivars (Lane A1: Am strain; Lane B1: Wi82 strain;and Lane C1: CL strain) as described above. As shown in FIG. 1, thismethod allows for a sensitive analysis of Glycine max that is capable ofdistinguishing between cultivar strains. Gel analysis measures forspecies specificity as determined by product formation (indicated byarrow) as well as for cultivar specificity as determined by DNA size.The benefit of using polymorphic repeat markers is that differences inrepeat lengths usually occur during natural strain evolution in thewild, allowing for the genetic fingerprint of different strains orcultivars. For MOR-1117, gene sequencing of the marker determined thefragment to contain a 173 bp segment with a polynucleotide repeatconsisting of 20 CA-dinucleotides in tandem. Analysis of this marker inthe different cultivars (FIG. 1, Lane A1: 169 bp; Lane B1 173 bp; LaneC1 175 bp) demonstrates its ability to identify plant type and cultivarstrain. This approach is used for identifying markers in glyphosateresistant (GR) and glyphosate susceptible (GS) Conyza canadensis.

Example 2

[0108] Haplotype Analysis of Heterogeneous Populations of Plants forDiagnosis of Biotypes for Herbicide Resistance.

[0109] DNA from the genomes of HR and HS weeds are isolated from fieldspecimens and plated in semisolid medium or in soil treated with activelevels of herbicide. Seedlings from plants that are able to grow in thepresence of active herbicide levels are classified as herbicideresistant (HR). Those that are not able to grow in the presence ofactive herbicide levels are classified as herbicide susceptible (HS).DNAs from both classes are analyzed at the genome level using up to tenpolymorphic DNA markers to identify haplotype patterns that areassociated with susceptibility or resistance using methods described inExample 1. This approach has been used to identify DNA markers inGlycine max and Conyza canadensis for the identification of haplotypesthat are associated with certain phenotypes such as but not limited toflower color, herbicide resistance, etc. This approach now serves as amethod for distinguishing HR from HS biotypes and is useful for farmersto identify the presence of HR weeds in the crop fields to developing acrop management system prior to planting. The identification of HRassociated haplotypes in certain weed species will allow farmers toavoid certain herbicide management systems such as the no-till narrowspacing design used for Roundup Ready® crop plants such as soybeans.

Example 3

[0110] Generation of Glyphosate-Susceptible Conyza canadensis

[0111] Naturally occurring HR weeds such as Conyza canadensis are usefulfor identifying genes that are capable of allowing certain weeds tobecome resistant to a class of compounds in an attempt to uncover themechanism(s) of herbicide-resistance. Here we teach the use of employingmutagenesis strategies to glyphosate-resistant (GR) Conyza to generateglyphosate-susceptible (GS) strains that are useful for gene discovery.Briefly, GR Conyza canadensis seedlings are exposed to mutagens such as,but not limited to, mismatch repair inhibitors, chemical mutagens,radiation, etc., and seeds are plated on to solid Murashige and Skoog(MS) media in 150 mm dishes with and without active levels of herbicide.One such example is the use of the small molecule inhibitor of mismatchrepair called Morphocene™, and other chemical inhibitors of mismatchrepair as described in PCT Publication No. WO 02/054856 (which isincorporated herein by reference). Morphocene™ has been demonstrated toblock the endogenous mismatch repair machinery of plants, includingArabidopsis thaliana and Glycine max, leading to genome wide mutationsand the production of offspring with new phenotypes. After treatment,one hundred seedlings are moved to two-gallon pots containing metromix200 soil (Scotts-Sierra Horticultural Products Company, Marysville,Ohio). Plants are grown to maturity (referred to as founder plants) ingrowth rooms for 12-16 weeks, a time at which Conyza mature and produceseeds. Each plant is capable of producing 200,000 to 300,000 seeds.Seeds are harvested separately from each plant and stored in 4° C.dessicators. Roughly 20,000 seeds from each founder plant is plated ontogrowth plates containing optimal levels of glyphosate as determined bytitration curves. Seedlings are scored glyphosate-susceptible if any ofthe following features contrast with the parental plant: bleaching (lossof chlorophyll coloration), stunted root formation, or stunted shootheight. Mutant plants are traced back to the appropriate founder andexpanded to produce glyphosate-susceptible (GS) offspring. GS plants arethen analyzed using a variety of gene expression methods to identifygenes whose expression is altered or through standard gene mappingmethods using DNA markers to map loci that are linked to the resistantor susceptible phenotypes. The demonstrated ability to generateglyphosate-susceptible Conyza from naturally glyphosate-resistantparental plants allows for the generation of subtypes that can beanalyzed by comparative genetics to identify altered gene(s) that conferglyphosate-resistance. This is approach offers certain advantages overmethods that employ mutagenesis to GS wild-type strains to identifythose that are GR. The generation of GS offspring from GR offspring isnow used to identify altered genes responsible for conferring GS from GRparental strains.

[0112] Discussion: The results described above will lead to severalconclusions. The identification of genomic markers in heterogeneous weedspecies consisting of subsets that are susceptible and resistant tocertain herbicides are useful for identifying HR weeds at the genomiclevel for aiding in crop management decisions. The use of breedingherbicide resistant and susceptible forms can be used to identify linkedgenetic loci to identify genes involved to herbicide resistance. Themutagenesis of naturally occurring herbicide resistant weeds are usefulfor identifying genes involved in resistance to a certain class ofcompound.

Example 4

[0113] Isolation of DNA Markers for Haplotype Analysis of Horseweeds forGenomic Identification of Herbicide Resistant Biotypes

[0114] Isolation and modification of the genomic DNA: Total horseweed(Conyza Canadensis) genomic DNA was isolated from 100 mg of leaves usingPlant DNAZol as described by the manufacturer (Invitrogen). The typicalyield was 10-20 μg DNA per preparation. Two different biotypes ofhorseweed were used as source of the DNA and were designated HR and HS.HR has been confirmed to exhibit glyphosate tolerance while HS issensitive to glyphosate treatment.

[0115] DNAs were digested with two restriction enzymes, and theresulting DNA fragments were ligated with adapters simultaneously inbuffer (50 mM Tris-HCl, 10 mM MgCl₂, 10 mM DTT, 1 mM ATP, pH 7.5, 50 mMNaCl, 45 μg/ml BSA). 10 units of each restriction enzyme were used todigest 2.5 μg DNA. 1.5 units of T4 DNA ligase, 2-10 pmoles of Adapter 1(for one restriction enzyme) and 2-10 pmoles of Adapter 2 (for secondrestriction enzyme) were also added. Incubation was performed in thetotal volume of 22 μl at 37° C. for 2 hr.

[0116] Preparation of adapters: The following are the sequences of theadapters: Adapter 1 5′-GACGATGAGTCCTGAG-3′ (SEQ ID NO:1)3′-TACTCAGGACTCAT-5′ (SEQ ID NO:2) Adapter 2 5′-CTCGTAGACTGCGTACC-3′(SEQ ID NO:3) 3′-CATCTGACGCATGGTTAA-5′ (SEQ ID NO:4)

[0117] To prepare 50 pmoles/μl of Adapter 1, equal volume of 100 μM ofthe 16-mer 5′-GACGATGAGTCCTGAG-3′ SEQ ID NO: 1) and the 14-mer5′-TACTCAGGACTCAT-3′ SEQ ID NO: 2) were mixed, incubated at 85° C. for 5min. and slowly cooled to room temperature. 50 pmoles/μl of Adapter 2was prepared in the same way by mixing the 16-mer5′-CTCGTAGACTGCGTACC-3′ SEQ ID NO: 3) and 17-mer5′-AATTGGTACGCAGTCTAC-3′ SEQ ID NO: 4).

[0118] The DNAs modified as above were used for two rounds of PCR(pre-amplification and selective amplification).

[0119] Pre-amplification of fragments: In pre-amplification, primers 2-0and 1-C dissolved at 10 mM in ddH₂O were used. 2-0 primer:5′-CTCGTAGACTGCGTACCAATTC (SEQ ID NO:5) 1-C primer:5′-GACGATGAGTCCTGAGTACC (SEQ ID NO:6)

[0120] The reaction was performed as follows: 2.5 μl of ½ dilution ofmodified DNA template, 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 2 mM MgCl₂,0.001% gelatin, 200 μM dNTPs, 6 pmoles of primers 2-0 and 1-C, 0.5 unitsof Taq DNA polymerase in the total volume of 20 μl.

[0121] The amplification was performed in Hybaid Omni thermal cycler.The cycle profile was as follows:  1 cycle: denaturation: 94° C., 2 min20 cycles: denaturation: 94° C., 20 seconds annealing: 56° C., 30seconds extension: 72° C., 2 min  1 cycle: 72° C., 2 min  1 cycle: 60°C., 30 min

[0122] Selective amplification of fragments: Selective amplification wasperformed as follows: 5 μl of {fraction (1/20)} dilution ofpreamplification product, 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 2 mMMgCl₂, 0.001% gelatin, 200 μM dNTPs, 6 pmoles of primer 2-TG (labeledwith fluorescence dye) and primer 1-CAC, 0.5 units of Taq DNA polymerasein the total volume of 20 μl. 2-TG primer:5′-CTCGTAGACTGCGTACCAATTCTG-3′ (SEQ ID NO:7) 1-CAC primer:5′-GACGATGAGTCCTGAGTACCAC-3′ (SEQ ID NO:8)

[0123] The amplification was performed in Hybaid Omni thermal cycler.The cycle profile was as follows:  1 cycle: denaturation: 94° C., 2 min10 cycles: denaturation: 94° C., 20 seconds annealing: 66° C., 30seconds (decrease 1° C./cylce) extension: 72° C., 2 min 20 cycles:denaturation: 94° C., 20 seconds annealing: 56° C., 30 secondsextension: 72° C., 2 min  1 cycle: 60° C., 30 min

[0124] Gel analysis of amplified fragments: After selectiveamplification, the reaction products were analyzed on Beckman CEQ2000XLsequencing machine. DNA size standard 400 was used for the fragmentanalysis. {fraction (1/50)} dilution of DNA size standard was made insample loading buffer (Deionized formamide), 8 μl of amplified fragmentswere added to 25 μl of diluted DNA size standard and loaded ontoCEQ2000XL with capillary temperature at 50° C., sample denaturation at90° C. for 2 min injection at 2 kV 30 seconds and separation at 6 kV 35min. The results of the analysis are shown in FIG. 2. The top panel isthe fluorescence histogram of HR DNA and bottom panel is the one for HSDNA. A 140 bp fragment was identified to be present only in HR butabsent in HS horseweed genomic DNA (arrow).

[0125] Cloning of the Polymorphic Fragment: To clone this fragment,selective amplification was performed as above with the exception of2-TG primer not being labeled with dye and the products were separatedon 20% polyacrylamide gel. The bands with the size around 140 bp wereisolated with Qiagen PCR purification kit (Qiagen) and cloned into TAcloning vector (Invitrogen) as described by manufacturer. More than 20clones were picked and sequenced. The clones with the insert sizematching expected 140 bp were chosen and their inserts were used asprobes in Southern blot analysis to identify which clone represents theband present in HR but absent in HS. Amplified products from HR and HSwere separated on 2.5% agarose gel and transferred onto N-Hybond+membrane (Amersham) by standard blotting procedures using 20×SSC as thetransfer buffer. Each membrane will be incubated at 55° C. in 10 ml ofhybridization solution (North2South non-radioactive detection kit,Pierce) containing 100 ng of cloned insert DNA probes, which weregenerated by PCR amplification and gel purification, and labeledaccording to the manufacturer's directions. Membranes were washed threetimes in 2×SSC, 0.1% SDS at 55° C., and three times in 2×SSC at ambienttemperature. Detection of hybridized probes was carried out usingenhanced chemiluminescence (ECL) and autoradiography.

[0126] One class of the clones met such criteria and Southern blotanalysis is presented in FIG. 3. Lane 1 and 3 are amplified productsfrom HS while lane 2 and 4 are those from HR. Lane 5 is the insert fromthe clone. Lane 1 and 2 are amplified with dye-labeled 2-TG primer whilelane 3 and 4 with 2-TG not labeled with dye. The sequence of this clonewas determined.

[0127] Determination of Flanking Sequences of the Polymorphic Fragment:To obtain the sequences upstream and downstream of this fragment in thegenome, the thermal asymmetric interlaced (TAIL) PCR method wasperformed on HR genomic DNA as described by Liu et al. (1995) The PlantJournal 8(3):457-463). The primers used were: AD3 (degenerate primer):WGTGNAGWANCANAGA (SEQ ID NO:9) 1-F: 5′-CACATCTTTAGCATCGGC-3 (SEQ IDNO:10) 2-F: 5′-AAAGTGGCTGAATCGTGG-3′ (SEQ ID NO:11) 3-F:5′-GATTTGAATGGTGGTGCC-3′ (SEQ ID NO:12) 1-R: 5′-GGCACCACCATTCAAATC-3′(SEQ ID NO:13) 2-R: 5′-ATACCACGATTCAGCCAC-3′ (SEQ ID NO:14) 3-R:5′-GCCGATGCTAAAGATGTG-3′ (SEQ ID NO:15)

[0128] TAIL-PCR products were cloned into TA cloning vector (Invitrogen)and sequenced to obtain the flanking sequences of the polymorphicfragment.

[0129] Assembly of the DNA Marker: A contig was assembled from all threesequences. The presence of this contig was confirmed by PCR using HR DNAas template and two primers spanning the three fragments in the contig.Interestingly, no product was amplified using these same two primerswith HS DNA as the template. The sequence of this contig is shown in SEQID NO: 16. The contig encodes a protein of unknown nature (partial openreading frame without stop codon) (shown in SEQ ID NO: 17). Thepolymorphic marker was designated MOR9.

Example 5

[0130] Haplotype Analysis of Heterogeneous Populations of Plants forDiagnosis of Biotypes for Herbicide Resistance

[0131] Design of Primers for Diagnosis with the DNA Marker: PCR Primer 1(SEQ ID NO: 18) and 2 (SEQ ID NO: 19) were designed based on thesequence of the DNA marker obtained in Example 4. Control PCR Primer 1(SEQ ID NO: 20) and 2 (SEQ ID NO: 21) are primers that will amplify afragment in all horseweed biotypes. PCR Primer 1: 5′-TTG TCG CTG TCC AACCAT TG-3′ (SEQ ID NO:18) PCR Primer 2: 5′-TTG GCA TGG TCT GTA GCT GG-3′(SEQ ID NO:19) Control PCR Primer 1: 5′-CCA TCG TAT CAT CAT GTG C-3′(SEQ ID NO:20) Control PCR Primer 2: 5′-TGC AAT ATG TTA AAG TAG AGC-3′(SEQ ID NO:21)

[0132] Analysis of the DNA Marker: Horseweeds were either germinatedfrom seeds or seedlings were transferred from the field into thegreenhouse. DNAs from the genomes of HR and HS horseweeds were isolated.At the same time, glyphosate was applied at 2 lb active ingredient/acrerate to confirm the plants' sensitivity to the herbicide.

[0133] Using HR or HS genomic DNAs as templates, PCR amplification wasperformed in 67 mM Tris pH 8.8, 16.6 mM NH₄ SO₄, 6.7 mM MgCl₂, 100 mMβ-mercaptoethanol, 6.7 μM EDTA pH 8.0, 6% DMSO, 1.25 mM dNTPs and 1.25units Taq polymerase with the total volume of 25 μl and cycled at 1×94°C., 2 min; 45×94° C., 30 sec; 56° C. 30 sec; 72° C., 1.5 min; 1×72° C.,10 min. For the MOR9 marker assay, 20 pmoles of PCR Primer 1 (SEQ ID NO:18) and PCR Primer 2 (SEQ ID NO: 19) were used while Control PCR Primer1 (SEQ ID NO: 20) and Control PCR Primer 2 (SEQ ID NO: 21) were used incontrol experiment.

[0134] A typical result is shown in FIG. 4. Lanes 1-3 are theamplification products for the MOR9 marker, while lanes 4-6 are theamplification products for control marker. The templates for lanes 1 and4 are DNA from glyphosate-tolerant horseweed, the templates for lanes 2and 5 are from glyphosate-sensitive horseweed, and the templates forlanes 3 and 6 are water controls (i.e., without any DNA).

[0135] In total, 30 biotypes (7 HS and 23 HR) were analyzed using 74 HRand 32 HS plants. There is 100% correlation of the absence of MOR9marker with HS and 88% correlation of the presence with HR (Table 1).TABLE 1 Horseweed Glyphosate Common MOR9 Biotype Resistance PCR MarkerMarker Correlation 13D + + + + 2D + + + + 3M + + + + 25D + + + +18D + + + + 12M + + + + 17D + + + + 19M + + + + 16M + + + + 15D + + + +27 + + + + 14M + + + + 9D + + + + 22M + + + + 5M + + + + 10D + + − −11D + + − − 4M − + − + 28 − + − + Home − + − + HR − + − + WF − + − + WS− + − + MT − + − +

Example 5

[0136] Homologs of MOR9:

[0137] Homolog 1: Two homologs of MOR9 clone were identified. Homolog 1was cloned by regular PCR with two primers. During the diagnostic assayof the MOR9 marker, a pair of primers was shown to amplify a 281 bpproduct with the genomic DNA from glyphosate-sensitive and toleranthorseweed. The PCR condition was the same as that used to amplify MOR9in the diagnostic assay in Example 4. The sequences of the two primersare: Primer 1: 5′-CACATCTTTAGCATCGGC-3′ (SEQ ID NO:62) Primer 2:5′-TCATTCGGAGAAACATCATG-3′ (SEQ ID NO:63)

[0138] The 281 bp PCR products were sequenced and shown to be the samein both glyphosate-sensitive and tolerant horseweed. The sequence showedsignificant homology (>62%) to MOR9 DNA marker and was named as MOR9Homolog 1 (MOR9 H1). The nucleotide sequence of MOR9 H1 is shown in SEQID NO: 60. An alignment of the overlapping regions of MOR9 (SEQ ID NO:126) and MOR9 H1 (SEQ ID NO: 127) is as follows (differences in thesequences are noted in boldface): MOR9 Marker CACATCTTTA GCATCGGCCACCATTGAAAA AGTGGCTGAA TCGTGGTATA MOR9 H1 CACATCTTTA GCATCGGCCACCATTGAAAA AGTGGCTGAA TCATGGGATA 51                                                 100 MOR9 MarkerAGAATGTTGT ATTGCAGGTT GATGTTGAGA GGGATTTGGA TGATTTGAAT MOR9 H1AAAATGTCGC TACAAGTGTT GATGATGGTA GGGACTTGAA TGATTCTAAT 101                                                150 MOR9 MarkerGGTGGTG.CC AGAATTCTAC TGCTGAGTCA TCTTTGCATG ATTTCCATGC MOR9 H1GGTGATGGCC TTCACTCGAC TGTTGAACCA ACATTGCGTG GTTTGCATGC 151                                                200 MOR9 MarkerAAAAGGTGGT GCTACTCATG TTTCCCCTAT GCTTGATCCT CCTAAGTTTC MOR9 H1ATATGTTGGT GATTCTAATG TACCTCCAA. .A.....C.. .CAAAGTTCC 201                                                250 MOR9 MarkerCTCCTGGTAC TACTTATTTT AAGCCAGCTA CAGACACATG CCAATGACAT MOR9 H1CTCCTGATGC TTCTTATTTT CAACCGGCTG CATGT.CATG CAAATGACAT 251                                              298 MOR9 MarkerTCTTGATGTT .......... .......... .......... ........ MOR9 H1 TCACCCTGCTACAGATGAGG CCCCTTTGCA TGATGTTTCT CCGAATGA

[0139] Homolog 2: A second homolog of MOR9 was discovered by RT-PCR.First, RNA was extracted from horseweed (glyphosate susceptible orresistant) and reverse transcribed with adapter-T25VN (AAG CAG TGG TATCAA CGC AGA GTA CTT TTT TTT TTT TTT TTT TTT TTT TTV N) (SEQ ID NO: 64)primer under standard RT conditions. HWMOR 9-RACE1F primer (CAC ATC TTTAGC ATC GGC CAC CAT TG) (SEQ ID NO: 65), primer CTA ATA CGA CTC ACT ATAGGG CAA GCA GTG GTA TCA ACG CAG AGT (SEQ ID NO: 66) and primer CTA ATACGA CTC ACT ATA GGG C (SEQ ID NO: 67) were used to amplify from reversetranscribed product under the following amplification conditions:  5cycles: 94° C., 30 sec 72° C., 3 min  5 cycles: 94° C., 30 sec 70° C.,30 sec 72° C., 3 min decrease (0.5° C./cycle) 25 cycles: 94° C., 30 sec68° C., 30 sec; 72° C., 3 min

[0140] A second round of PCR was performed on diluted primary PCRproduct with HWMOR9-FACE2F (GTG GCT GAA TCG TGG TAT AAG AAT G) (SEQ IDNO: 68) and nested primer (AAG CAG TGG TAT CAA CGC AGA GT) (SEQ ID NO:69) under the following amplification conditions:

[0141] 20 cycles: 94° C., 30 sec; 68° C., 30 sec; 72° C., 3 min.

[0142] A PCR product was found and sequenced that also showed homologyto MOR9 and MOR9 H1. The second homolog was named MOR9 Homolog 2 (MOR9H2) and the nucleic acid sequence of MOR9 H2 is shown in SEQ ID NO: 61.An alignment of the overlapping regions of MOR9 (SEQ ID NO: 126) and theMOR9 H1 (SEQ ID NO: 127) and MOR9 H2 (SEQ ID NO: 128) is as follows(differences between the homologs and MOR9 are shown in boldface;differences between the homologs are indicated by an underline): 1                                                   50 MOR9 CACATCTTTAGCATCGGCCA CCATTGAAAA AGTGGCTGAA TCGTGGTATA MOR9 H1 CACATCTTTAGCATCGGCCA CCATTGAAAA AGTGGCTGAA TCATGGGATA MOR9 H2 .................... .......... .......... .......... 51                                                 100 MOR9 AGAATGTTGTATTGCAGGTT GATGTTGAGA GGGATTTGGA TGATTTGAAT MOR9 H1 AAAATGTCGCTACAAGTGTT GATGATGGTA GGGACTTGAA TGATTCTAAT MOR9 H2 .................... ....ATGGTA GGGATTTGAA TGATTC G A C T 101                                                150 MOR9 GGTGGTG.CCAGAATTCTAC TGCTGAGTCA TCTTTGCATG ATTTCCATGC MOR9 H1 GGTGATGGCCTTCACTCGAC TGTTGAACCA ACATTGCGTG GTTTGCATGC MOR9 H2 GG G GATGGC T  T ACACTCGAC TGCTGAACCA ACATTGCATG GTTTGCATGC 151                                                200 MOR9 AAAAGGTGGTGCTACTCATG TTTCCCCTAT GCTTGATCCT CCTAAGTTTC MOR9 H1 ATATGTTGGTGATTCTAATG TACCTCCAA. .A.....C.. .CAAAGTTCC MOR9 H2 AAATGTTG A T GATT GTA C TG T G CCTCCTAT GCCGGAACCG  CCAAAGTTCC 201                                                250 MOR9 CTCCTGGTACTACTTATTTT AAGCCAGCTA CAGACACATG CCAATGACAT MOR9 H1 CTCCTGATGCTTCTTATTTT CAACCGGCTG CATGT.CATG CAAATGACAT MOR9 H2 CTCCTGATGC TACTTA CTTT CAGCCGGCTG CATGT.CATG T AAATGACAT 251                                                300 MOR9 TCTTGATGTT.......... .......... .......... .......... MOR9 H1 TCACCCTGCTACAGATGAGG CCCCTT.TGC ATGATGTTTC TCCGAATGA. MOR9 H2 TCA T CCTGCTTCACATGAGG CCCCTTATGC ATGATGTTAC TCCTAATGAT 301                                                350 MOR9 .................... .......... .......... .......... MOR9 H1 .................... .......... .......... .......... MOR9 H2 CTTAGTGGATACCCTGACAG TCCTAAGGTC CAGCAGCCGC GTACTTATGC 351                                                400 MOR9 .................... .......... .......... .......... MOR9 H1 .................... .......... .......... .......... MOR9 H2 TTCTATCTTTCAGGATGCGG CTAACATCAA CAAGAAAGGT AAATTGAGAT  401                     423MOR9 .......... .......... ... MOR9 H1 .......... .......... ... MOR9 H2TCATCCCTCC AAAAAAAAAA AAA

[0143] A pair of primers was designed and used for PCR amplification ofboth glyphosate susceptible and glyphosate resistant horseweed. Theresult was shown in FIG. 7 which indicates that MOR9 H2 is present inboth biotypes.

Example 6

[0144] Cloning of the GA repeat from horseweed: Adapter-ligated PCR wasused to identify GA repeat sequences from horseweed. Briefly, genomicDNA was extracted as described in Example 4 and digested with either asingle restriction enzyme or a combination of enzymes. Then a mixture ofprimer adapters for the restriction enzymes recognition sequences (forsingle enzyme digestion or combination enzyme digestion) were ligated torestricted DNA fragments. Sequence of the primers used was as follows: Aprimer: 5′-GTAATACGACTCACTATAGGGCACGCG- (SEQ ID NO:70)TGGTCGACGGCCCGGGCTGGT-3′ B primer: 5′-AATTACCAGCCC-NH2 (SEQ ID NO:71) Cprimer: 5′-GATCACCAGCCC-NH2 (SEQ ID NO:72) D primer: 5′-AGCTACCAGCCC-NH2(SEQ ID NO:73)

[0145] The ligation products were used as templates for primary PCRamplification with the following primer: AP1 and GAGB or AP1 and GAH.AP1: 5′-GTAATACGACTCACTATAGGGC-3′ (SEQ ID NO:74) GAGB:5′-GAGAGAGAGAGAGAGAGAGAGB-3′ (SEQ ID NO:75) GAH:5′-GAGAGAGAGAGAGAGAGAGAH-3′ (SEQ ID NO:76)

[0146] The primary PCR condition is as follows:  5 cycles: 94° C., 30seconds; 65° C., (decrease 1° C., after each cycle) 30 seconds, 72° C.,3 minutes 40 cycles: 94° C., 30 seconds, 60° C., 30 seconds, 72° C. 3minutes  1 cycle: 72° C., 10 minutes.

[0147] The primary PCR product was diluted {fraction (1/50)} with waterand used at {fraction (1/1000)} for secondary PCR amplification whichused primer AP2 (SEQ ID NO: 77) and GAGB (SEQ ID NO: 75) or AP2 (SEQ IDNO: 77) and GAH (SEQ ID NO: 76). The sequence of Primer AP2 is asfollows:

[0148] AP2: ACTATAGGGCACGCGTGGT (SEQ ID NO: 77)

[0149] The secondary PCR products were cloned into TA cloning vector(Invitrogen) and sequences downstream of GA repeats were determined.

[0150] To identify the sequences upstream of GA repeat, two nestedprimers (NP1 and NP2) for each of the HGA clones based on the determineddownstream sequences were designed and used to repeat the primary PCRwith AP1 and NP1 as above using the same ligation products. Thesequences of the specific NP1 and NP2 primers is as follows: NP1-HGA1:5′-CCATCGTATCATCATGTGC-3′ (SEQ ID NO:113) NP2-HGA1:5′-TAGCTTGCAAAAGTTCTG-3′ (SEQ ID NO:114) NP1-HGA2:5′-TACCAATATTGCCCTTGG-3′ (SEQ ID NO:116) NP2-HGA2:5′-GTATACCCTTTTCCGTTCC-3′ (SEQ ID NO:117) NP1-HGA3:5′-TACCCAACCCTATCTFFCC-3′ (SEQ ID NO:119) NP2-HGA3:5′-TCCATTCATTCTTCACCC-3′ (SEQ ID NO:120) NP1-HGA4:5′-ATGTTAGTGTTCTACACC-3′ (SEQ ID NO:122) NP2-HGA4:5′-CTTAGATACGTAACAACC-3′ (SEQ ID NO:123) NP1-HGA5:5′-AACGACTCTTCCAAACCC-3′ (SEQ ID NO:124) NP2-HGA5:5′-TGACCTCAATTGACTTGC-3′ (SEQ ID NO:125)

[0151] Then a secondary PCR amplification was performed with AP2 (SEQ IDNO: 77) and NP2 primers. The final products were cloned and sequenced todetermine the upstream sequence of a particular clone on which the NP1and NP2 was based. The sequences of upstream and downstream regions wereassembled into one contig and used for designing primers to amplify thesimple sequence repeat (SSR) marker.

[0152] Five complete markers were assembled and their sequences are HGA1(SEQ ID NO: 78); HGA2 (SEQ ID NO: 79); HGA3 (SEQ ID NO: 80); HGA4 (SEQID NO: 81); HGA5 (SEQ ID NO: 82).

[0153] Primers were designed to assay for polymorphisms betweendifferent biotypes of horseweed for each of the HGA sequences. Examplesof sequences of diagnostic primers for HGA sequences are as follows:D-HGA1: 5′-TGCAATATGTTAAAGTAGAGC-3′ (SEQ ID NO:115) D-HGA2:5′-TTCATGGTGATGACTCGGCAGC3′ (SEQ ID NO:118) D-HGA3:5′-CCATAATTTGGTGTAAGAATC-3′ (SEQ ID NO:121) D-HGA5:5′-ATATAGACATCCATTCCA-3′ (SEQ ID NO:126)

[0154] Amplifications were performed using the diagnostic primers forthe GHA sequences with either the NP1 primers or NP2 primers. Nopolymorphisms were found when assaying for the HGA1, HGA2, or HGA3markers using the four different horseweed collections available (FIG.7).

1 129 1 16 DNA Artificial Sequence Oligonucleotide primer 1 gacgatgagtcctgag 16 2 14 DNA Artificial Sequence Oligonucleotide primer 2tactcaggac tcat 14 3 17 DNA Artificial Sequence Oligonucleotide primer 3ctcgtagact gcgtacc 17 4 18 DNA Artificial Sequence Oligonucleotideprimer 4 aattggtacg cagtctac 18 5 22 DNA Artificial SequenceOligonucleotide primer 5 ctcgtagact gcgtaccaat tc 22 6 20 DNA ArtificialSequence Oligonucleotide primer 6 gacgatgagt cctgagtacc 20 7 24 DNAArtificial Sequence Oligonucleotide primer 7 ctcgtagact gcgtaccaat tctg24 8 22 DNA Artificial Sequence Oligonucleotide primer 8 gacgatgagtcctgagtacc ac 22 9 16 DNA Artificial Sequence Degenerate oligonucleotideprimer 9 ngtgnagnan canaga 16 10 18 DNA Artificial SequenceOligonucleotide primer 10 cacatcttta gcatcggc 18 11 18 DNA ArtificialSequence Oligonucleotide primer 11 aaagtggctg aatcgtgg 18 12 18 DNAArtificial Sequence Oligonucleotide primer 12 gatttgaatg gtggtgcc 18 1318 DNA Artificial Sequence Oligonucleotide primer 13 ggcaccacca ttcaaatc18 14 18 DNA Artificial Sequence Oligonucleotide primer 14 ataccacgattcagccac 18 15 18 DNA Artificial Sequence Oligonucleotide primer 15gccgatgcta aagatgtg 18 16 919 DNA Conyza sp. 16 ataccacgat tcagccaccatacaaccgcc gcctgatcaa ttgaaggctg gggggggatt 60 cgattgtggg tggggcagttccaaatctca ctattgatgc tcaattaatc tatttagggg 120 ttttgcaaac cgaaaccctaatataaaaac cttaatttgt tgcttgtcgc tgtccaacca 180 ttgtccaccc ttctctgaaccacagtttgg aaatttaatt gatggggagg gagatttttc 240 gaacctggat ggcaattgattactcactta gccacaagtt gatgaagtgg atcgcatatt 300 ggccaaaaag gtcattttcatgtgccgtca tgtgaagata gtgaacaaat tgatgatata 360 tttaccatct ttaaggatgaaatggaaatg tttaatgata ctgataatcc actctctaaa 420 gatcaagtgg ccgaattgaatagaatttta gttgtacatt gggctaaaat cactaatttt 480 gagggctcga attcacagcaacgaccttta cttccggatg aaattgaaaa gcattttggt 540 gttcaacctt gtgacaatattaacacatct ttagcatcgg ccaccattga aaaagtggct 600 gaatcgtggt ataagaatgttgtattgcag gttgatgttg agagggattt ggatgatttg 660 aatggtggtg ccagaattctactgctgagt catctttgca tgatttccat gcaaaaggtg 720 gtgctactca tgtttcccctatgcttgatc ctcctaagtt tcctcctggt actacttatt 780 ttaagccagc tacagaccatgccaatgaca ttcttgatgt ttcagatgat gttcctaagc 840 atgatgtttc tccgaatgatcttggtggac atccagatag ccccaaaact cagcagcctc 900 acttctgtgc ttctccaca 91917 179 PRT Conyza sp. 17 Met Glu Met Phe Asn Asp Thr Asp Asn Pro Leu SerLys Asp Gln Val 1 5 10 15 Ala Glu Leu Asn Arg Ile Leu Val Val His TrpAla Lys Ile Thr Asn 20 25 30 Phe Glu Gly Ser Asn Ser Gln Gln Arg Pro LeuLeu Pro Asp Glu Ile 35 40 45 Glu Lys His Phe Gly Val Gln Pro Cys Asp AsnIle Asn Thr Ser Leu 50 55 60 Ala Ser Ala Thr Ile Glu Lys Val Ala Glu SerTrp Tyr Lys Asn Val 65 70 75 80 Val Leu Gln Val Asp Val Glu Arg Asp LeuAsp Asp Leu Asn Gly Gly 85 90 95 Ala Arg Ile Leu Leu Leu Ser His Leu CysMet Ile Ser Met Gln Lys 100 105 110 Val Val Leu Leu Met Phe Pro Leu CysLeu Ile Leu Leu Ser Phe Leu 115 120 125 Leu Val Leu Leu Ile Leu Ser GlnLeu Gln Thr Met Pro Met Thr Phe 130 135 140 Leu Met Phe Gln Met Met PheLeu Ser Met Met Phe Leu Arg Met Ile 145 150 155 160 Leu Val Asp Ile GlnIle Ala Pro Lys Leu Ser Ser Leu Thr Ser Val 165 170 175 Leu Leu His 1820 DNA Artificial Sequence Oligonucleotide primer 18 ttgtcgctgtccaaccattg 20 19 20 DNA Artificial Sequence Oligonucleotide primer 19ttggcatggt ctgtagctgg 20 20 19 DNA Artificial Sequence Oligonucleotideprimer 20 ccatcgtatc atcatgtgc 19 21 21 DNA Artificial SequenceOligonucleotide primer 21 tgcaatatgt taaagtagag c 21 22 3218 DNASaccharomyces cerevisiae 22 aaataggaat gtgatacctt ctattgcatg caaagatagtgtaggaggcg ctgctattgc 60 caaagacttt tgagaccgct tgctgtttca ttatagttgaggagttctcg aagacgagaa 120 attagcagtt ttcggtgttt agtaatcgcg ctagcatgctaggacaattt aactgcaaaa 180 ttttgatacg atagtgatag taaatggaag gtaaaaataacatagaccta tcaataagca 240 atgtctctca gaataaaagc acttgatgca tcagtggttaacaaaattgc tgcaggtgag 300 atcataatat cccccgtaaa tgctctcaaa gaaatgatggagaattccat cgatgcgaat 360 gctacaatga ttgatattct agtcaaggaa ggaggaattaaggtacttca aataacagat 420 aacggatctg gaattaataa agcagacctg ccaatcttatgtgagcgatt cacgacgtcc 480 aaattacaaa aattcgaaga tttgagtcag attcaaacgtatggattccg aggagaagct 540 ttagccagta tctcacatgt ggcaagagtc acagtaacgacaaaagttaa agaagacaga 600 tgtgcatgga gagtttcata tgcagaaggt aagatgttggaaagccccaa acctgttgct 660 ggaaaagacg gtaccacgat cctagttgaa gacctttttttcaatattcc ttctagatta 720 agggccttga ggtcccataa tgatgaatac tctaaaatattagatgttgt cgggcgatac 780 gccattcatt ccaaggacat tggcttttct tgtaaaaagttcggagactc taattattct 840 ttatcagtta aaccttcata tacagtccag gataggattaggactgtgtt caataaatct 900 gtggcttcga atttaattac ttttcatatc agcaaagtagaagatttaaa cctggaaagc 960 gttgatggaa aggtgtgtaa tttgaatttc atatccaaaaagtccatttc attaattttt 1020 ttcattaata atagactagt gacatgtgat cttctaagaagagctttgaa cagcgtttac 1080 tccaattatc tgccaaaggg cttcagacct tttatttatttgggaattgt tatagatccg 1140 gcggctgttg atgttaacgt tcacccgaca aagagagaggttcgtttcct gagccaagat 1200 gagatcatag agaaaatcgc caatcaattg cacgccgaattatctgccat tgatacttca 1260 cgtactttca aggcttcttc aatttcaaca aacaagccagagtcattgat accatttaat 1320 gacaccatag aaagtgatag gaataggaag agtctccgacaagcccaagt ggtagagaat 1380 tcatatacga cagccaatag tcaactaagg aaagcgaaaagacaagagaa taaactagtc 1440 agaatagatg cttcacaagc taaaattacg tcatttttatcctcaagtca acagttcaac 1500 tttgaaggat cgtctacaaa gcgacaactg agtgaacccaaggtaacaaa tgtaagccac 1560 tcccaagagg cagaaaagct gacactaaat gaaagcgaacaaccgcgtga tgccaataca 1620 atcaatgata atgacttgaa ggatcaacct aagaagaaacaaaagttggg ggattataaa 1680 gttccaagca ttgccgatga cgaaaagaat gcactcccgatttcaaaaga cgggtatatt 1740 agagtaccta aggagcgagt taatgttaat cttacgagtatcaagaaatt gcgtgaaaaa 1800 gtagatgatt cgatacatcg agaactaaca gacatttttgcaaatttgaa ttacgttggg 1860 gttgtagatg aggaaagaag attagccgct attcagcatgacttaaagct ttttttaata 1920 gattacggat ctgtgtgcta tgagctattc tatcagattggtttgacaga cttcgcaaac 1980 tttggtaaga taaacctaca gagtacaaat gtgtcagatgatatagtttt gtataatctc 2040 ctatcagaat ttgacgagtt aaatgacgat gcttccaaagaaaaaataat tagtaaaata 2100 tgggacatga gcagtatgct aaatgagtac tattccatagaattggtgaa tgatggtcta 2160 gataatgact taaagtctgt gaagctaaaa tctctaccactacttttaaa aggctacatt 2220 ccatctctgg tcaagttacc attttttata tatcgcctgggtaaagaagt tgattgggag 2280 gatgaacaag agtgtctaga tggtatttta agagagattgcattactcta tatacctgat 2340 atggttccga aagtcgatac actcgatgca tcgttgtcagaagacgaaaa agcccagttt 2400 ataaatagaa aggaacacat atcctcatta ctagaacacgttctcttccc ttgtatcaaa 2460 cgaaggttcc tggcccctag acacattctc aaggatgtcgtggaaatagc caaccttcca 2520 gatctataca aagtttttga gaggtgttaa ctttaaaacgttttggctgt aataccaaag 2580 tttttgttta tttcctgagt gtgattgtgt ttcatttgaaagtgtatgcc ctttccttta 2640 acgattcatc cgcgagattt caaaggatat gaaatatggttgcagttagg aaagtatgtc 2700 agaaatgtat attcggattg aaactcttct aatagttctgaagtcacttg gttccgtatt 2760 gttttcgtcc tcttcctcaa gcaacgattc ttgtctaagcttattcaacg gtaccaaaga 2820 cccgagtcct tttatgagag aaaacatttc atcatttttcaactcaatta tcttaatatc 2880 attttgtagt attttgaaaa caggatggta aaacgaatcacctgaatcta gaagctgtac 2940 cttgtcccat aaaagtttta atttactgag cctttcggtcaagtaaacta gtttatctag 3000 ttttgaaccg aatattgtgg gcagatttgc agtaagttcagttagatcta ctaaaagttg 3060 tttgacagca gccgattcca caaaaatttg gtaaaaggagatgaaagaga cctcgcgcgt 3120 aatggtttgc atcaccatcg gatgtctgtt gaaaaactcactttttgcat ggaagttatt 3180 aacaataaga ctaatgatta ccttagaata atgtataa3218 23 769 PRT Saccharomyces cerevisiae 23 Met Ser Leu Arg Ile Lys AlaLeu Asp Ala Ser Val Val Asn Lys Ile 1 5 10 15 Ala Ala Gly Glu Ile IleIle Ser Pro Val Asn Ala Leu Lys Glu Met 20 25 30 Met Glu Asn Ser Ile AspAla Asn Ala Thr Met Ile Asp Ile Leu Val 35 40 45 Lys Glu Gly Gly Ile LysVal Leu Gln Ile Thr Asp Asn Gly Ser Gly 50 55 60 Ile Asn Lys Ala Asp LeuPro Ile Leu Cys Glu Arg Phe Thr Thr Ser 65 70 75 80 Lys Leu Gln Lys PheGlu Asp Leu Ser Gln Ile Gln Thr Tyr Gly Phe 85 90 95 Arg Gly Glu Ala LeuAla Ser Ile Ser His Val Ala Arg Val Thr Val 100 105 110 Thr Thr Lys ValLys Glu Asp Arg Cys Ala Trp Arg Val Ser Tyr Ala 115 120 125 Glu Gly LysMet Leu Glu Ser Pro Lys Pro Val Ala Gly Lys Asp Gly 130 135 140 Thr ThrIle Leu Val Glu Asp Leu Phe Phe Asn Ile Pro Ser Arg Leu 145 150 155 160Arg Ala Leu Arg Ser His Asn Asp Glu Tyr Ser Lys Ile Leu Asp Val 165 170175 Val Gly Arg Tyr Ala Ile His Ser Lys Asp Ile Gly Phe Ser Cys Lys 180185 190 Lys Phe Gly Asp Ser Asn Tyr Ser Leu Ser Val Lys Pro Ser Tyr Thr195 200 205 Val Gln Asp Arg Ile Arg Thr Val Phe Asn Lys Ser Val Ala SerAsn 210 215 220 Leu Ile Thr Phe His Ile Ser Lys Val Glu Asp Leu Asn LeuGlu Ser 225 230 235 240 Val Asp Gly Lys Val Cys Asn Leu Asn Phe Ile SerLys Lys Ser Ile 245 250 255 Ser Leu Ile Phe Phe Ile Asn Asn Arg Leu ValThr Cys Asp Leu Leu 260 265 270 Arg Arg Ala Leu Asn Ser Val Tyr Ser AsnTyr Leu Pro Lys Gly Phe 275 280 285 Arg Pro Phe Ile Tyr Leu Gly Ile ValIle Asp Pro Ala Ala Val Asp 290 295 300 Val Asn Val His Pro Thr Lys ArgGlu Val Arg Phe Leu Ser Gln Asp 305 310 315 320 Glu Ile Ile Glu Lys IleAla Asn Gln Leu His Ala Glu Leu Ser Ala 325 330 335 Ile Asp Thr Ser ArgThr Phe Lys Ala Ser Ser Ile Ser Thr Asn Lys 340 345 350 Pro Glu Ser LeuIle Pro Phe Asn Asp Thr Ile Glu Ser Asp Arg Asn 355 360 365 Arg Lys SerLeu Arg Gln Ala Gln Val Val Glu Asn Ser Tyr Thr Thr 370 375 380 Ala AsnSer Gln Leu Arg Lys Ala Lys Arg Gln Glu Asn Lys Leu Val 385 390 395 400Arg Ile Asp Ala Ser Gln Ala Lys Ile Thr Ser Phe Leu Ser Ser Ser 405 410415 Gln Gln Phe Asn Phe Glu Gly Ser Ser Thr Lys Arg Gln Leu Ser Glu 420425 430 Pro Lys Val Thr Asn Val Ser His Ser Gln Glu Ala Glu Lys Leu Thr435 440 445 Leu Asn Glu Ser Glu Gln Pro Arg Asp Ala Asn Thr Ile Asn AspAsn 450 455 460 Asp Leu Lys Asp Gln Pro Lys Lys Lys Gln Lys Leu Gly AspTyr Lys 465 470 475 480 Val Pro Ser Ile Ala Asp Asp Glu Lys Asn Ala LeuPro Ile Ser Lys 485 490 495 Asp Gly Tyr Ile Arg Val Pro Lys Glu Arg ValAsn Val Asn Leu Thr 500 505 510 Ser Ile Lys Lys Leu Arg Glu Lys Val AspAsp Ser Ile His Arg Glu 515 520 525 Leu Thr Asp Ile Phe Ala Asn Leu AsnTyr Val Gly Val Val Asp Glu 530 535 540 Glu Arg Arg Leu Ala Ala Ile GlnHis Asp Leu Lys Leu Phe Leu Ile 545 550 555 560 Asp Tyr Gly Ser Val CysTyr Glu Leu Phe Tyr Gln Ile Gly Leu Thr 565 570 575 Asp Phe Ala Asn PheGly Lys Ile Asn Leu Gln Ser Thr Asn Val Ser 580 585 590 Asp Asp Ile ValLeu Tyr Asn Leu Leu Ser Glu Phe Asp Glu Leu Asn 595 600 605 Asp Asp AlaSer Lys Glu Lys Ile Ile Ser Lys Ile Trp Asp Met Ser 610 615 620 Ser MetLeu Asn Glu Tyr Tyr Ser Ile Glu Leu Val Asn Asp Gly Leu 625 630 635 640Asp Asn Asp Leu Lys Ser Val Lys Leu Lys Ser Leu Pro Leu Leu Leu 645 650655 Lys Gly Tyr Ile Pro Ser Leu Val Lys Leu Pro Phe Phe Ile Tyr Arg 660665 670 Leu Gly Lys Glu Val Asp Trp Glu Asp Glu Gln Glu Cys Leu Asp Gly675 680 685 Ile Leu Arg Glu Ile Ala Leu Leu Tyr Ile Pro Asp Met Val ProLys 690 695 700 Val Asp Thr Leu Asp Ala Ser Leu Ser Glu Asp Glu Lys AlaGln Phe 705 710 715 720 Ile Asn Arg Lys Glu His Ile Ser Ser Leu Leu GluHis Val Leu Phe 725 730 735 Pro Cys Ile Lys Arg Arg Phe Leu Ala Pro ArgHis Ile Leu Lys Asp 740 745 750 Val Val Glu Ile Ala Asn Leu Pro Asp LeuTyr Lys Val Phe Glu Arg 755 760 765 Cys 24 3056 DNA Mus musculus 24gaattccggt gaaggtcctg aagaatttcc agattcctga gtatcattgg aggagacaga 60taacctgtcg tcaggtaacg atggtgtata tgcaacagaa atgggtgttc ctggagacgc 120gtcttttccc gagagcggca ccgcaactct cccgcggtga ctgtgactgg aggagtcctg 180catccatgga gcaaaccgaa ggcgtgagta cagaatgtgc taaggccatc aagcctattg 240atgggaagtc agtccatcaa atttgttctg ggcaggtgat actcagttta agcaccgctg 300tgaaggagtt gatagaaaat agtgtagatg ctggtgctac tactattgat ctaaggctta 360aagactatgg ggtggacctc attgaagttt cagacaatgg atgtggggta gaagaagaaa 420actttgaagg tctagctctg aaacatcaca catctaagat tcaagagttt gccgacctca 480cgcaggttga aactttcggc tttcgggggg aagctctgag ctctctgtgt gcactaagtg 540atgtcactat atctacctgc cacgggtctg caagcgttgg gactcgactg gtgtttgacc 600ataatgggaa aatcacccag aaaactccct acccccgacc taaaggaacc acagtcagtg 660tgcagcactt attttataca ctacccgtgc gttacaaaga gtttcagagg aacattaaaa 720aggagtattc caaaatggtg caggtcttac aggcgtactg tatcatctca gcaggcgtcc 780gtgtaagctg cactaatcag ctcggacagg ggaagcggca cgctgtggtg tgcacaagcg 840gcacgtctgg catgaaggaa aatatcgggt ctgtgtttgg ccagaagcag ttgcaaagcc 900tcattccttt tgttcagctg ccccctagtg acgctgtgtg tgaagagtac ggcctgagca 960cttcaggacg ccacaaaacc ttttctacgt ttcgggcttc atttcacagt gcacgcacgg 1020cgccgggagg agtgcaacag acaggcagtt tttcttcatc aatcagaggc cctgtgaccc 1080agcaaaggtc tctaagcttg tcaatgaggt tttatcacat gtataaccgg catcagtacc 1140catttgtcgt ccttaacgtt tccgttgact cagaatgtgt ggatattaat gtaactccag 1200ataaaaggca aattctacta caagaagaga agctattgct ggccgtttta aagacctcct 1260tgataggaat gtttgacagt gatgcaaaca agcttaatgt caaccagcag ccactgctag 1320atgttgaagg taacttagta aagctgcata ctgcagaact agaaaagcct gtgccaggaa 1380agcaagataa ctctccttca ctgaagagca cagcagacga gaaaagggta gcatccatct 1440ccaggctgag agaggccttt tctcttcatc ctactaaaga gatcaagtct aggggtccag 1500agactgctga actgacacgg agttttccaa gtgagaaaag gggcgtgtta tcctcttatc 1560cttcagacgt catctcttac agaggcctcc gtggctcgca ggacaaattg gtgagtccca 1620cggacagccc tggtgactgt atggacagag agaaaataga aaaagactca gggctcagca 1680gcacctcagc tggctctgag gaagagttca gcaccccaga agtggccagt agctttagca 1740gtgactataa cgtgagctcc ctagaagaca gaccttctca ggaaaccata aactgtggtg 1800acctggactg ccgtcctcca ggtacaggac agtccttgaa gccagaagac catggatatc 1860aatgcaaagc tctacctcta gctcgtctgt cacccacaaa tgccaagcgc ttcaagacag 1920aggaaagacc ctcaaatgtc aacatttctc aaagattgcc tggtcctcag agcacctcag 1980cagctgaggt cgatgtagcc ataaaaatga ataagagaat cgtgctcctc gagttctctc 2040tgagttctct agctaagcga atgaagcagt tacagcacct aaaggcgcag aacaaacatg 2100aactgagtta cagaaaattt agggccaaga tttgccctgg agaaaaccaa gcagcagaag 2160atgaactcag aaaagagatt agtaaatcga tgtttgcaga gatggagatc ttgggtcagt 2220ttaacctggg atttatagta accaaactga aagaggacct cttcctggtg gaccagcatg 2280ctgcggatga gaagtacaac tttgagatgc tgcagcagca cacggtgctc caggcgcaga 2340ggctcatcac accccagact ctgaacttaa ctgctgtcaa tgaagctgta ctgatagaaa 2400atctggaaat attcagaaag aatggctttg actttgtcat tgatgaggat gctccagtca 2460ctgaaagggc taaattgatt tccttaccaa ctagtaaaaa ctggaccttt ggaccccaag 2520atatagatga actgatcttt atgttaagtg acagccctgg ggtcatgtgc cggccctcac 2580gagtcagaca gatgtttgct tccagagcct gtcggaagtc agtgatgatt ggaacggcgc 2640tcaatgcgag cgagatgaag aagctcatca cccacatggg tgagatggac cacccctgga 2700actgccccca cggcaggcca accatgaggc acgttgccaa tctggatgtc atctctcaga 2760actgacacac cccttgtagc atagagttta ttacagattg ttcggtttgc aaagagaagg 2820ttttaagtaa tctgattatc gttgtacaaa aattagcatg ctgctttaat gtactggatc 2880catttaaaag cagtgttaag gcaggcatga tggagtgttc ctctagctca gctacttggg 2940tgatccggtg ggagctcatg tgagcccagg actttgagac cactccgagc cacattcatg 3000agactcaatt caaggacaaa aaaaaaaaga tatttttgaa gccttttaaa aaaaaa 3056 25859 PRT Mus musculus 25 Met Glu Gln Thr Glu Gly Val Ser Thr Glu Cys AlaLys Ala Ile Lys 1 5 10 15 Pro Ile Asp Gly Lys Ser Val His Gln Ile CysSer Gly Gln Val Ile 20 25 30 Leu Ser Leu Ser Thr Ala Val Lys Glu Leu IleGlu Asn Ser Val Asp 35 40 45 Ala Gly Ala Thr Thr Ile Asp Leu Arg Leu LysAsp Tyr Gly Val Asp 50 55 60 Leu Ile Glu Val Ser Asp Asn Gly Cys Gly ValGlu Glu Glu Asn Phe 65 70 75 80 Glu Gly Leu Ala Leu Lys His His Thr SerLys Ile Gln Glu Phe Ala 85 90 95 Asp Leu Thr Gln Val Glu Thr Phe Gly PheArg Gly Glu Ala Leu Ser 100 105 110 Ser Leu Cys Ala Leu Ser Asp Val ThrIle Ser Thr Cys His Gly Ser 115 120 125 Ala Ser Val Gly Thr Arg Leu ValPhe Asp His Asn Gly Lys Ile Thr 130 135 140 Gln Lys Thr Pro Tyr Pro ArgPro Lys Gly Thr Thr Val Ser Val Gln 145 150 155 160 His Leu Phe Tyr ThrLeu Pro Val Arg Tyr Lys Glu Phe Gln Arg Asn 165 170 175 Ile Lys Lys GluTyr Ser Lys Met Val Gln Val Leu Gln Ala Tyr Cys 180 185 190 Ile Ile SerAla Gly Val Arg Val Ser Cys Thr Asn Gln Leu Gly Gln 195 200 205 Gly LysArg His Ala Val Val Cys Thr Ser Gly Thr Ser Gly Met Lys 210 215 220 GluAsn Ile Gly Ser Val Phe Gly Gln Lys Gln Leu Gln Ser Leu Ile 225 230 235240 Pro Phe Val Gln Leu Pro Pro Ser Asp Ala Val Cys Glu Glu Tyr Gly 245250 255 Leu Ser Thr Ser Gly Arg His Lys Thr Phe Ser Thr Phe Arg Ala Ser260 265 270 Phe His Ser Ala Arg Thr Ala Pro Gly Gly Val Gln Gln Thr GlySer 275 280 285 Phe Ser Ser Ser Ile Arg Gly Pro Val Thr Gln Gln Arg SerLeu Ser 290 295 300 Leu Ser Met Arg Phe Tyr His Met Tyr Asn Arg His GlnTyr Pro Phe 305 310 315 320 Val Val Leu Asn Val Ser Val Asp Ser Glu CysVal Asp Ile Asn Val 325 330 335 Thr Pro Asp Lys Arg Gln Ile Leu Leu GlnGlu Glu Lys Leu Leu Leu 340 345 350 Ala Val Leu Lys Thr Ser Leu Ile GlyMet Phe Asp Ser Asp Ala Asn 355 360 365 Lys Leu Asn Val Asn Gln Gln ProLeu Leu Asp Val Glu Gly Asn Leu 370 375 380 Val Lys Leu His Thr Ala GluLeu Glu Lys Pro Val Pro Gly Lys Gln 385 390 395 400 Asp Asn Ser Pro SerLeu Lys Ser Thr Ala Asp Glu Lys Arg Val Ala 405 410 415 Ser Ile Ser ArgLeu Arg Glu Ala Phe Ser Leu His Pro Thr Lys Glu 420 425 430 Ile Lys SerArg Gly Pro Glu Thr Ala Glu Leu Thr Arg Ser Phe Pro 435 440 445 Ser GluLys Arg Gly Val Leu Ser Ser Tyr Pro Ser Asp Val Ile Ser 450 455 460 TyrArg Gly Leu Arg Gly Ser Gln Asp Lys Leu Val Ser Pro Thr Asp 465 470 475480 Ser Pro Gly Asp Cys Met Asp Arg Glu Lys Ile Glu Lys Asp Ser Gly 485490 495 Leu Ser Ser Thr Ser Ala Gly Ser Glu Glu Glu Phe Ser Thr Pro Glu500 505 510 Val Ala Ser Ser Phe Ser Ser Asp Tyr Asn Val Ser Ser Leu GluAsp 515 520 525 Arg Pro Ser Gln Glu Thr Ile Asn Cys Gly Asp Leu Asp CysArg Pro 530 535 540 Pro Gly Thr Gly Gln Ser Leu Lys Pro Glu Asp His GlyTyr Gln Cys 545 550 555 560 Lys Ala Leu Pro Leu Ala Arg Leu Ser Pro ThrAsn Ala Lys Arg Phe 565 570 575 Lys Thr Glu Glu Arg Pro Ser Asn Val AsnIle Ser Gln Arg Leu Pro 580 585 590 Gly Pro Gln Ser Thr Ser Ala Ala GluVal Asp Val Ala Ile Lys Met 595 600 605 Asn Lys Arg Ile Val Leu Leu GluPhe Ser Leu Ser Ser Leu Ala Lys 610 615 620 Arg Met Lys Gln Leu Gln HisLeu Lys Ala Gln Asn Lys His Glu Leu 625 630 635 640 Ser Tyr Arg Lys PheArg Ala Lys Ile Cys Pro Gly Glu Asn Gln Ala 645 650 655 Ala Glu Asp GluLeu Arg Lys Glu Ile Ser Lys Ser Met Phe Ala Glu 660 665 670 Met Glu IleLeu Gly Gln Phe Asn Leu Gly Phe Ile Val Thr Lys Leu 675 680 685 Lys GluAsp Leu Phe Leu Val Asp Gln His Ala Ala Asp Glu Lys Tyr 690 695 700 AsnPhe Glu Met Leu Gln Gln His Thr Val Leu Gln Ala Gln Arg Leu 705 710 715720 Ile Thr Pro Gln Thr Leu Asn Leu Thr Ala Val Asn Glu Ala Val Leu 725730 735 Ile Glu Asn Leu Glu Ile Phe Arg Lys Asn Gly Phe Asp Phe Val Ile740 745 750 Asp Glu Asp Ala Pro Val Thr Glu Arg Ala Lys Leu Ile Ser LeuPro 755 760 765 Thr Ser Lys Asn Trp Thr Phe Gly Pro Gln Asp Ile Asp GluLeu Ile 770 775 780 Phe Met Leu Ser Asp Ser Pro Gly Val Met Cys Arg ProSer Arg Val 785 790 795 800 Arg Gln Met Phe Ala Ser Arg Ala Cys Arg LysSer Val Met Ile Gly 805 810 815 Thr Ala Leu Asn Ala Ser Glu Met Lys LysLeu Ile Thr His Met Gly 820 825 830 Glu Met Asp His Pro Trp Asn Cys ProHis Gly Arg Pro Thr Met Arg 835 840 845 His Val Ala Asn Leu Asp Val IleSer Gln Asn 850 855 26 2771 DNA Homo sapiens 26 cgaggcggat cgggtgttgcatccatggag cgagctgaga gctcgagtac agaacctgct 60 aaggccatca aacctattgatcggaagtca gtccatcaga tttgctctgg gcaggtggta 120 ctgagtctaa gcactgcggtaaaggagtta gtagaaaaca gtctggatgc tggtgccact 180 aatattgatc taaagcttaaggactatgga gtggatctta ttgaagtttc agacaatgga 240 tgtggggtag aagaagaaaacttcgaaggc ttaactctga aacatcacac atctaagatt 300 caagagtttg ccgacctaactcaggttgaa acttttggct ttcgggggga agctctgagc 360 tcactttgtg cactgagcgatgtcaccatt tctacctgcc acgcatcggc gaaggttgga 420 actcgactga tgtttgatcacaatgggaaa attatccaga aaacccccta cccccgcccc 480 agagggacca cagtcagcgtgcagcagtta ttttccacac tacctgtgcg ccataaggaa 540 tttcaaagga atattaagaaggagtatgcc aaaatggtcc aggtcttaca tgcatactgt 600 atcatttcag caggcatccgtgtaagttgc accaatcagc ttggacaagg aaaacgacag 660 cctgtggtat gcacaggtggaagccccagc ataaaggaaa atatcggctc tgtgtttggg 720 cagaagcagt tgcaaagcctcattcctttt gttcagctgc cccctagtga ctccgtgtgt 780 gaagagtacg gtttgagctgttcggatgct ctgcataatc ttttttacat ctcaggtttc 840 atttcacaat gcacgcatggagttggaagg agttcaacag acagacagtt tttctttatc 900 aaccggcggc cttgtgacccagcaaaggtc tgcagactcg tgaatgaggt ctaccacatg 960 tataatcgac accagtatccatttgttgtt cttaacattt ctgttgattc agaatgcgtt 1020 gatatcaatg ttactccagataaaaggcaa attttgctac aagaggaaaa gcttttgttg 1080 gcagttttaa agacctctttgataggaatg tttgatagtg atgtcaacaa gctaaatgtc 1140 agtcagcagc cactgctggatgttgaaggt aacttaataa aaatgcatgc agcggatttg 1200 gaaaagccca tggtagaaaagcaggatcaa tccccttcat taaggactgg agaagaaaaa 1260 aaagacgtgt ccatttccagactgcgagag gccttttctc ttcgtcacac aacagagaac 1320 aagcctcaca gcccaaagactccagaacca agaaggagcc ctctaggaca gaaaaggggt 1380 atgctgtctt ctagcacttcaggtgccatc tctgacaaag gcgtcctgag acctcagaaa 1440 gaggcagtga gttccagtcacggacccagt gaccctacgg acagagcgga ggtggagaag 1500 gactcggggc acggcagcacttccgtggat tctgaggggt tcagcatccc agacacgggc 1560 agtcactgca gcagcgagtatgcggccagc tccccagggg acaggggctc gcaggaacat 1620 gtggactctc aggagaaagcgcctgaaact gacgactctt tttcagatgt ggactgccat 1680 tcaaaccagg aagataccggatgtaaattt cgagttttgc ctcagccaac taatctcgca 1740 accccaaaca caaagcgttttaaaaaagaa gaaattcttt ccagttctga catttgtcaa 1800 aagttagtaa atactcaggacatgtcagcc tctcaggttg atgtagctgt gaaaattaat 1860 aagaaagttg tgcccctggacttttctatg agttctttag ctaaacgaat aaagcagtta 1920 catcatgaag cacagcaaagtgaaggggaa cagaattaca ggaagtttag ggcaaagatt 1980 tgtcctggag aaaatcaagcagccgaagat gaactaagaa aagagataag taaaacgatg 2040 tttgcagaaa tggaaatcattggtcagttt aacctgggat ttataataac caaactgaat 2100 gaggatatct tcatagtggaccagcatgcc acggacgaga agtataactt cgagatgctg 2160 cagcagcaca ccgtgctccaggggcagagg ctcatagcac ctcagactct caacttaact 2220 gctgttaatg aagctgttctgatagaaaat ctggaaatat ttagaaagaa tggctttgat 2280 tttgttatcg atgaaaatgctccagtcact gaaagggcta aactgatttc cttgccaact 2340 agtaaaaact ggaccttcggaccccaggac gtcgatgaac tgatcttcat gctgagcgac 2400 agccctgggg tcatgtgccggccttcccga gtcaagcaga tgtttgcctc cagagcctgc 2460 cggaagtcgg tgatgattgggactgctctt aacacaagcg agatgaagaa actgatcacc 2520 cacatggggg agatggaccacccctggaac tgtccccatg gaaggccaac catgagacac 2580 atcgccaacc tgggtgtcatttctcagaac tgaccgtagt cactgtatgg aataattggt 2640 tttatcgcag atttttatgttttgaaagac agagtcttca ctaacctttt ttgttttaaa 2700 atgaaacctg ctacttaaaaaaaatacaca tcacacccat ttaaaagtga tcttgagaac 2760 cttttcaaac c 2771 27932 PRT Homo sapiens 27 Met Lys Gln Leu Pro Ala Ala Thr Val Arg Leu LeuSer Ser Ser Gln 1 5 10 15 Ile Ile Thr Ser Val Val Ser Val Val Lys GluLeu Ile Glu Asn Ser 20 25 30 Leu Asp Ala Gly Ala Thr Ser Val Asp Val LysLeu Glu Asn Tyr Gly 35 40 45 Phe Asp Lys Ile Glu Val Arg Asp Asn Gly GluGly Ile Lys Ala Val 50 55 60 Asp Ala Pro Val Met Ala Met Lys Tyr Tyr ThrSer Lys Ile Asn Ser 65 70 75 80 His Glu Asp Leu Glu Asn Leu Thr Thr TyrGly Phe Arg Gly Glu Ala 85 90 95 Leu Gly Ser Ile Cys Cys Ile Ala Glu ValLeu Ile Thr Thr Arg Thr 100 105 110 Ala Ala Asp Asn Phe Ser Thr Gln TyrVal Leu Asp Gly Ser Gly His 115 120 125 Ile Leu Ser Gln Lys Pro Ser HisLeu Gly Gln Gly Thr Thr Val Thr 130 135 140 Ala Leu Arg Leu Phe Lys AsnLeu Pro Val Arg Lys Gln Phe Tyr Ser 145 150 155 160 Thr Ala Lys Lys CysLys Asp Glu Ile Lys Lys Ile Gln Asp Leu Leu 165 170 175 Met Ser Phe GlyIle Leu Lys Pro Asp Leu Arg Ile Val Phe Val His 180 185 190 Asn Lys AlaVal Ile Trp Gln Lys Ser Arg Val Ser Asp His Lys Met 195 200 205 Ala LeuMet Ser Val Leu Gly Thr Ala Val Met Asn Asn Met Glu Ser 210 215 220 PheGln Tyr His Ser Glu Glu Ser Gln Ile Tyr Leu Ser Gly Phe Leu 225 230 235240 Pro Lys Cys Asp Ala Asp His Ser Phe Thr Ser Leu Ser Thr Pro Glu 245250 255 Arg Ser Phe Ile Phe Ile Asn Ser Arg Pro Val His Gln Lys Asp Ile260 265 270 Leu Lys Leu Ile Arg His His Tyr Asn Leu Lys Cys Leu Lys GluSer 275 280 285 Thr Arg Leu Tyr Pro Val Phe Phe Leu Lys Ile Asp Val ProThr Ala 290 295 300 Asp Val Asp Val Asn Leu Thr Pro Asp Lys Ser Gln ValLeu Leu Gln 305 310 315 320 Asn Lys Glu Ser Val Leu Ile Ala Leu Glu AsnLeu Met Thr Thr Cys 325 330 335 Tyr Gly Pro Leu Pro Ser Thr Asn Ser TyrGlu Asn Asn Lys Thr Asp 340 345 350 Val Ser Ala Ala Asp Ile Val Leu SerLys Thr Ala Glu Thr Asp Val 355 360 365 Leu Phe Asn Lys Val Glu Ser SerGly Lys Asn Tyr Ser Asn Val Asp 370 375 380 Thr Ser Val Ile Pro Phe GlnAsn Asp Met His Asn Asp Glu Ser Gly 385 390 395 400 Lys Asn Thr Asp AspCys Leu Asn His Gln Ile Ser Ile Gly Asp Phe 405 410 415 Gly Tyr Gly HisCys Ser Ser Glu Ile Ser Asn Ile Asp Lys Asn Thr 420 425 430 Lys Asn AlaPhe Gln Asp Ile Ser Met Ser Asn Val Ser Trp Glu Asn 435 440 445 Ser GlnThr Glu Tyr Ser Lys Thr Cys Phe Ile Ser Ser Val Lys His 450 455 460 ThrGln Ser Glu Asn Gly Asn Lys Asp His Ile Asp Glu Ser Gly Glu 465 470 475480 Asn Glu Glu Glu Ala Gly Leu Glu Asn Ser Ser Glu Ile Ser Ala Asp 485490 495 Glu Trp Ser Arg Gly Asn Ile Leu Lys Asn Ser Val Gly Glu Asn Ile500 505 510 Glu Pro Val Lys Ile Leu Val Pro Glu Lys Ser Leu Pro Cys LysVal 515 520 525 Ser Asn Asn Asn Tyr Pro Ile Pro Glu Gln Met Asn Leu AsnGlu Asp 530 535 540 Ser Cys Asn Lys Lys Ser Asn Val Ile Asp Asn Lys SerGly Lys Val 545 550 555 560 Thr Ala Tyr Asp Leu Leu Ser Asn Arg Val IleLys Lys Pro Met Ser 565 570 575 Ala Ser Ala Leu Phe Val Gln Asp His ArgPro Gln Phe Leu Ile Glu 580 585 590 Asn Pro Lys Thr Ser Leu Glu Asp AlaThr Leu Gln Ile Glu Glu Leu 595 600 605 Trp Lys Thr Leu Ser Glu Glu GluLys Leu Lys Tyr Glu Glu Lys Ala 610 615 620 Thr Lys Asp Leu Glu Arg TyrAsn Ser Gln Met Lys Arg Ala Ile Glu 625 630 635 640 Gln Glu Ser Gln MetSer Leu Lys Asp Gly Arg Lys Lys Ile Lys Pro 645 650 655 Thr Ser Ala TrpAsn Leu Ala Gln Lys His Lys Leu Lys Thr Ser Leu 660 665 670 Ser Asn GlnPro Lys Leu Asp Glu Leu Leu Gln Ser Gln Ile Glu Lys 675 680 685 Arg ArgSer Gln Asn Ile Lys Met Val Gln Ile Pro Phe Ser Met Lys 690 695 700 AsnLeu Lys Ile Asn Phe Lys Lys Gln Asn Lys Val Asp Leu Glu Glu 705 710 715720 Lys Asp Glu Pro Cys Leu Ile His Asn Leu Arg Phe Pro Asp Ala Trp 725730 735 Leu Met Thr Ser Lys Thr Glu Val Met Leu Leu Asn Pro Tyr Arg Val740 745 750 Glu Glu Ala Leu Leu Phe Lys Arg Leu Leu Glu Asn His Lys LeuPro 755 760 765 Ala Glu Pro Leu Glu Lys Pro Ile Met Leu Thr Glu Ser LeuPhe Asn 770 775 780 Gly Ser His Tyr Leu Asp Val Leu Tyr Lys Met Thr AlaAsp Asp Gln 785 790 795 800 Arg Tyr Ser Gly Ser Thr Tyr Leu Ser Asp ProArg Leu Thr Ala Asn 805 810 815 Gly Phe Lys Ile Lys Leu Ile Pro Gly ValSer Ile Thr Glu Asn Tyr 820 825 830 Leu Glu Ile Glu Gly Met Ala Asn CysLeu Pro Phe Tyr Gly Val Ala 835 840 845 Asp Leu Lys Glu Ile Leu Asn AlaIle Leu Asn Arg Asn Ala Lys Glu 850 855 860 Val Tyr Glu Cys Arg Pro ArgLys Val Ile Ser Tyr Leu Glu Gly Glu 865 870 875 880 Ala Val Arg Leu SerArg Gln Leu Pro Met Tyr Leu Ser Lys Glu Asp 885 890 895 Ile Gln Asp IleIle Tyr Arg Met Lys His Gln Phe Gly Asn Glu Ile 900 905 910 Lys Glu CysVal His Gly Arg Pro Phe Phe His His Leu Thr Tyr Leu 915 920 925 Pro GluThr Thr 930 28 3063 DNA Homo sapiens 28 ggcacgagtg gctgcttgcg gctagtggatggtaattgcc tgcctcgcgc tagcagcaag 60 ctgctctgtt aaaagcgaaa atgaaacaattgcctgcggc aacagttcga ctcctttcaa 120 gttctcagat catcacttcg gtggtcagtgttgtaaaaga gcttattgaa aactccttgg 180 atgctggtgc cacaagcgta gatgttaaactggagaacta tggatttgat aaaattgagg 240 tgcgagataa cggggagggt atcaaggctgttgatgcacc tgtaatggca atgaagtact 300 acacctcaaa aataaatagt catgaagatcttgaaaattt gacaacttac ggttttcgtg 360 gagaagcctt ggggtcaatt tgttgtatagctgaggtttt aattacaaca agaacggctg 420 ctgataattt tagcacccag tatgttttagatggcagtgg ccacatactt tctcagaaac 480 cttcacatct tggtcaaggt acaactgtaactgctttaag attatttaag aatctacctg 540 taagaaagca gttttactca actgcaaaaaaatgtaaaga tgaaataaaa aagatccaag 600 atctcctcat gagctttggt atccttaaacctgacttaag gattgtcttt gtacataaca 660 aggcagttat ttggcagaaa agcagagtatcagatcacaa gatggctctc atgtcagttc 720 tggggactgc tgttatgaac aatatggaatcctttcagta ccactctgaa gaatctcaga 780 tttatctcag tggatttctt ccaaagtgtgatgcagacca ctctttcact agtctttcaa 840 caccagaaag aagtttcatc ttcataaacagtcgaccagt acatcaaaaa gatatcttaa 900 agttaatccg acatcattac aatctgaaatgcctaaagga atctactcgt ttgtatcctg 960 ttttctttct gaaaatcgat gttcctacagctgatgttga tgtaaattta acaccagata 1020 aaagccaagt attattacaa aataaggaatctgttttaat tgctcttgaa aatctgatga 1080 cgacttgtta tggaccatta cctagtacaaattcttatga aaataataaa acagatgttt 1140 ccgcagctga catcgttctt agtaaaacagcagaaacaga tgtgcttttt aataaagtgg 1200 aatcatctgg aaagaattat tcaaatgttgatacttcagt cattccattc caaaatgata 1260 tgcataatga tgaatctgga aaaaacactgatgattgttt aaatcaccag ataagtattg 1320 gtgactttgg ttatggtcat tgtagtagtgaaatttctaa cattgataaa aacactaaga 1380 atgcatttca ggacatttca atgagtaatgtatcatggga gaactctcag acggaatata 1440 gtaaaacttg ttttataagt tccgttaagcacacccagtc agaaaatggc aataaagacc 1500 atatagatga gagtggggaa aatgaggaagaagcaggtct tgaaaactct tcggaaattt 1560 ctgcagatga gtggagcagg ggaaatatacttaaaaattc agtgggagag aatattgaac 1620 ctgtgaaaat tttagtgcct gaaaaaagtttaccatgtaa agtaagtaat aataattatc 1680 caatccctga acaaatgaat cttaatgaagattcatgtaa caaaaaatca aatgtaatag 1740 ataataaatc tggaaaagtt acagcttatgatttacttag caatcgagta atcaagaaac 1800 ccatgtcagc aagtgctctt tttgttcaagatcatcgtcc tcagtttctc atagaaaatc 1860 ctaagactag tttagaggat gcaacactacaaattgaaga actgtggaag acattgagtg 1920 aagaggaaaa actgaaatat gaagagaaggctactaaaga cttggaacga tacaatagtc 1980 aaatgaagag agccattgaa caggagtcacaaatgtcact aaaagatggc agaaaaaaga 2040 taaaacccac cagcgcatgg aatttggcccagaagcacaa gttaaaaacc tcattatcta 2100 atcaaccaaa acttgatgaa ctccttcagtcccaaattga aaaaagaagg agtcaaaata 2160 ttaaaatggt acagatcccc ttttctatgaaaaacttaaa aataaatttt aagaaacaaa 2220 acaaagttga cttagaagag aaggatgaaccttgcttgat ccacaatctc aggtttcctg 2280 atgcatggct aatgacatcc aaaacagaggtaatgttatt aaatccatat agagtagaag 2340 aagccctgct atttaaaaga cttcttgagaatcataaact tcctgcagag ccactggaaa 2400 agccaattat gttaacagag agtctttttaatggatctca ttatttagac gttttatata 2460 aaatgacagc agatgaccaa agatacagtggatcaactta cctgtctgat cctcgtctta 2520 cagcgaatgg tttcaagata aaattgataccaggagtttc aattactgaa aattacttgg 2580 aaatagaagg aatggctaat tgtctcccattctatggagt agcagattta aaagaaattc 2640 ttaatgctat attaaacaga aatgcaaaggaagtttatga atgtagacct cgcaaagtga 2700 taagttattt agagggagaa gcagtgcgtctatccagaca attacccatg tacttatcaa 2760 aagaggacat ccaagacatt atctacagaatgaagcacca gtttggaaat gaaattaaag 2820 agtgtgttca tggtcgccca ttttttcatcatttaaccta tcttccagaa actacatgat 2880 taaatatgtt taagaagatt agttaccattgaaattggtt ctgtcataaa acagcatgag 2940 tctggtttta aattatcttt gtattatgtgtcacatggtt attttttaaa tgaggattca 3000 ctgacttgtt tttatattga aaaaagttccacgtattgta gaaaacgtaa ataaactaat 3060 aac 3063 29 932 PRT Homo sapiens29 Met Lys Gln Leu Pro Ala Ala Thr Val Arg Leu Leu Ser Ser Ser Gln 1 510 15 Ile Ile Thr Ser Val Val Ser Val Val Lys Glu Leu Ile Glu Asn Ser 2025 30 Leu Asp Ala Gly Ala Thr Ser Val Asp Val Lys Leu Glu Asn Tyr Gly 3540 45 Phe Asp Lys Ile Glu Val Arg Asp Asn Gly Glu Gly Ile Lys Ala Val 5055 60 Asp Ala Pro Val Met Ala Met Lys Tyr Tyr Thr Ser Lys Ile Asn Ser 6570 75 80 His Glu Asp Leu Glu Asn Leu Thr Thr Tyr Gly Phe Arg Gly Glu Ala85 90 95 Leu Gly Ser Ile Cys Cys Ile Ala Glu Val Leu Ile Thr Thr Arg Thr100 105 110 Ala Ala Asp Asn Phe Ser Thr Gln Tyr Val Leu Asp Gly Ser GlyHis 115 120 125 Ile Leu Ser Gln Lys Pro Ser His Leu Gly Gln Gly Thr ThrVal Thr 130 135 140 Ala Leu Arg Leu Phe Lys Asn Leu Pro Val Arg Lys GlnPhe Tyr Ser 145 150 155 160 Thr Ala Lys Lys Cys Lys Asp Glu Ile Lys LysIle Gln Asp Leu Leu 165 170 175 Met Ser Phe Gly Ile Leu Lys Pro Asp LeuArg Ile Val Phe Val His 180 185 190 Asn Lys Ala Val Ile Trp Gln Lys SerArg Val Ser Asp His Lys Met 195 200 205 Ala Leu Met Ser Val Leu Gly ThrAla Val Met Asn Asn Met Glu Ser 210 215 220 Phe Gln Tyr His Ser Glu GluSer Gln Ile Tyr Leu Ser Gly Phe Leu 225 230 235 240 Pro Lys Cys Asp AlaAsp His Ser Phe Thr Ser Leu Ser Thr Pro Glu 245 250 255 Arg Ser Phe IlePhe Ile Asn Ser Arg Pro Val His Gln Lys Asp Ile 260 265 270 Leu Lys LeuIle Arg His His Tyr Asn Leu Lys Cys Leu Lys Glu Ser 275 280 285 Thr ArgLeu Tyr Pro Val Phe Phe Leu Lys Ile Asp Val Pro Thr Ala 290 295 300 AspVal Asp Val Asn Leu Thr Pro Asp Lys Ser Gln Val Leu Leu Gln 305 310 315320 Asn Lys Glu Ser Val Leu Ile Ala Leu Glu Asn Leu Met Thr Thr Cys 325330 335 Tyr Gly Pro Leu Pro Ser Thr Asn Ser Tyr Glu Asn Asn Lys Thr Asp340 345 350 Val Ser Ala Ala Asp Ile Val Leu Ser Lys Thr Ala Glu Thr AspVal 355 360 365 Leu Phe Asn Lys Val Glu Ser Ser Gly Lys Asn Tyr Ser AsnVal Asp 370 375 380 Thr Ser Val Ile Pro Phe Gln Asn Asp Met His Asn AspGlu Ser Gly 385 390 395 400 Lys Asn Thr Asp Asp Cys Leu Asn His Gln IleSer Ile Gly Asp Phe 405 410 415 Gly Tyr Gly His Cys Ser Ser Glu Ile SerAsn Ile Asp Lys Asn Thr 420 425 430 Lys Asn Ala Phe Gln Asp Ile Ser MetSer Asn Val Ser Trp Glu Asn 435 440 445 Ser Gln Thr Glu Tyr Ser Lys ThrCys Phe Ile Ser Ser Val Lys His 450 455 460 Thr Gln Ser Glu Asn Gly AsnLys Asp His Ile Asp Glu Ser Gly Glu 465 470 475 480 Asn Glu Glu Glu AlaGly Leu Glu Asn Ser Ser Glu Ile Ser Ala Asp 485 490 495 Glu Trp Ser ArgGly Asn Ile Leu Lys Asn Ser Val Gly Glu Asn Ile 500 505 510 Glu Pro ValLys Ile Leu Val Pro Glu Lys Ser Leu Pro Cys Lys Val 515 520 525 Ser AsnAsn Asn Tyr Pro Ile Pro Glu Gln Met Asn Leu Asn Glu Asp 530 535 540 SerCys Asn Lys Lys Ser Asn Val Ile Asp Asn Lys Ser Gly Lys Val 545 550 555560 Thr Ala Tyr Asp Leu Leu Ser Asn Arg Val Ile Lys Lys Pro Met Ser 565570 575 Ala Ser Ala Leu Phe Val Gln Asp His Arg Pro Gln Phe Leu Ile Glu580 585 590 Asn Pro Lys Thr Ser Leu Glu Asp Ala Thr Leu Gln Ile Glu GluLeu 595 600 605 Trp Lys Thr Leu Ser Glu Glu Glu Lys Leu Lys Tyr Glu GluLys Ala 610 615 620 Thr Lys Asp Leu Glu Arg Tyr Asn Ser Gln Met Lys ArgAla Ile Glu 625 630 635 640 Gln Glu Ser Gln Met Ser Leu Lys Asp Gly ArgLys Lys Ile Lys Pro 645 650 655 Thr Ser Ala Trp Asn Leu Ala Gln Lys HisLys Leu Lys Thr Ser Leu 660 665 670 Ser Asn Gln Pro Lys Leu Asp Glu LeuLeu Gln Ser Gln Ile Glu Lys 675 680 685 Arg Arg Ser Gln Asn Ile Lys MetVal Gln Ile Pro Phe Ser Met Lys 690 695 700 Asn Leu Lys Ile Asn Phe LysLys Gln Asn Lys Val Asp Leu Glu Glu 705 710 715 720 Lys Asp Glu Pro CysLeu Ile His Asn Leu Arg Phe Pro Asp Ala Trp 725 730 735 Leu Met Thr SerLys Thr Glu Val Met Leu Leu Asn Pro Tyr Arg Val 740 745 750 Glu Glu AlaLeu Leu Phe Lys Arg Leu Leu Glu Asn His Lys Leu Pro 755 760 765 Ala GluPro Leu Glu Lys Pro Ile Met Leu Thr Glu Ser Leu Phe Asn 770 775 780 GlySer His Tyr Leu Asp Val Leu Tyr Lys Met Thr Ala Asp Asp Gln 785 790 795800 Arg Tyr Ser Gly Ser Thr Tyr Leu Ser Asp Pro Arg Leu Thr Ala Asn 805810 815 Gly Phe Lys Ile Lys Leu Ile Pro Gly Val Ser Ile Thr Glu Asn Tyr820 825 830 Leu Glu Ile Glu Gly Met Ala Asn Cys Leu Pro Phe Tyr Gly ValAla 835 840 845 Asp Leu Lys Glu Ile Leu Asn Ala Ile Leu Asn Arg Asn AlaLys Glu 850 855 860 Val Tyr Glu Cys Arg Pro Arg Lys Val Ile Ser Tyr LeuGlu Gly Glu 865 870 875 880 Ala Val Arg Leu Ser Arg Gln Leu Pro Met TyrLeu Ser Lys Glu Asp 885 890 895 Ile Gln Asp Ile Ile Tyr Arg Met Lys HisGln Phe Gly Asn Glu Ile 900 905 910 Lys Glu Cys Val His Gly Arg Pro PhePhe His His Leu Thr Tyr Leu 915 920 925 Pro Glu Thr Thr 930 30 3145 DNAHomo sapiens 30 ggcgggaaac agcttagtgg gtgtggggtc gcgcattttc ttcaaccaggaggtgaggag 60 gtttcgacat ggcggtgcag ccgaaggaga cgctgcagtt ggagagcgcggccgaggtcg 120 gcttcgtgcg cttctttcag ggcatgccgg agaagccgac caccacagtgcgccttttcg 180 accggggcga cttctatacg gcgcacggcg aggacgcgct gctggccgcccgggaggtgt 240 tcaagaccca gggggtgatc aagtacatgg ggccggcagg agcaaagaatctgcagagtg 300 ttgtgcttag taaaatgaat tttgaatctt ttgtaaaaga tcttcttctggttcgtcagt 360 atagagttga agtttataag aatagagctg gaaataaggc atccaaggagaatgattggt 420 atttggcata taaggcttct cctggcaatc tctctcagtt tgaagacattctctttggta 480 acaatgatat gtcagcttcc attggtgttg tgggtgttaa aatgtccgcagttgatggcc 540 agagacaggt tggagttggg tatgtggatt ccatacagag gaaactaggactgtgtgaat 600 tccctgataa tgatcagttc tccaatcttg aggctctcct catccagattggaccaaagg 660 aatgtgtttt acccggagga gagactgctg gagacatggg gaaactgagacagataattc 720 aaagaggagg aattctgatc acagaaagaa aaaaagctga cttttccacaaaagacattt 780 atcaggacct caaccggttg ttgaaaggca aaaagggaga gcagatgaatagtgctgtat 840 tgccagaaat ggagaatcag gttgcagttt catcactgtc tgcggtaatcaagtttttag 900 aactcttatc agatgattcc aactttggac agtttgaact gactacttttgacttcagcc 960 agtatatgaa attggatatt gcagcagtca gagcccttaa cctttttcagggttctgttg 1020 aagataccac tggctctcag tctctggctg ccttgctgaa taagtgtaaaacccctcaag 1080 gacaaagact tgttaaccag tggattaagc agcctctcat ggataagaacagaatagagg 1140 agagattgaa tttagtggaa gcttttgtag aagatgcaga attgaggcagactttacaag 1200 aagatttact tcgtcgattc ccagatctta accgacttgc caagaagtttcaaagacaag 1260 cagcaaactt acaagattgt taccgactct atcagggtat aaatcaactacctaatgtta 1320 tacaggctct ggaaaaacat gaaggaaaac accagaaatt attgttggcagtttttgtga 1380 ctcctcttac tgatcttcgt tctgacttct ccaagtttca ggaaatgatagaaacaactt 1440 tagatatgga tcaggtggaa aaccatgaat tccttgtaaa accttcatttgatcctaatc 1500 tcagtgaatt aagagaaata atgaatgact tggaaaagaa gatgcagtcaacattaataa 1560 gtgcagccag agatcttggc ttggaccctg gcaaacagat taaactggattccagtgcac 1620 agtttggata ttactttcgt gtaacctgta aggaagaaaa agtccttcgtaacaataaaa 1680 actttagtac tgtagatatc cagaagaatg gtgttaaatt taccaacagcaaattgactt 1740 ctttaaatga agagtatacc aaaaataaaa cagaatatga agaagcccaggatgccattg 1800 ttaaagaaat tgtcaatatt tcttcaggct atgtagaacc aatgcagacactcaatgatg 1860 tgttagctca gctagatgct gttgtcagct ttgctcacgt gtcaaatggagcacctgttc 1920 catatgtacg accagccatt ttggagaaag gacaaggaag aattatattaaaagcatcca 1980 ggcatgcttg tgttgaagtt caagatgaaa ttgcatttat tcctaatgacgtatactttg 2040 aaaaagataa acagatgttc cacatcatta ctggccccaa tatgggaggtaaatcaacat 2100 atattcgaca aactggggtg atagtactca tggcccaaat tgggtgttttgtgccatgtg 2160 agtcagcaga agtgtccatt gtggactgca tcttagcccg agtaggggctggtgacagtc 2220 aattgaaagg agtctccacg ttcatggctg aaatgttgga aactgcttctatcctcaggt 2280 ctgcaaccaa agattcatta ataatcatag atgaattggg aagaggaacttctacctacg 2340 atggatttgg gttagcatgg gctatatcag aatacattgc aacaaagattggtgcttttt 2400 gcatgtttgc aacccatttt catgaactta ctgccttggc caatcagataccaactgtta 2460 ataatctaca tgtcacagca ctcaccactg aagagacctt aactatgctttatcaggtga 2520 agaaaggtgt ctgtgatcaa agttttggga ttcatgttgc agagcttgctaatttcccta 2580 agcatgtaat agagtgtgct aaacagaaag ccctggaact tgaggagtttcagtatattg 2640 gagaatcgca aggatatgat atcatggaac cagcagcaaa gaagtgctatctggaaagag 2700 agcaaggtga aaaaattatt caggagttcc tgtccaaggt gaaacaaatgccctttactg 2760 aaatgtcaga agaaaacatc acaataaagt taaaacagct aaaagctgaagtaatagcaa 2820 agaataatag ctttgtaaat gaaatcattt cacgaataaa agttactacgtgaaaaatcc 2880 cagtaatgga atgaaggtaa tattgataag ctattgtctg taatagttttatattgtttt 2940 atattaaccc tttttccata gtgttaactg tcagtgccca tgggctatcaacttaataag 3000 atatttagta atattttact ttgaggacat tttcaaagat ttttattttgaaaaatgaga 3060 gctgtaactg aggactgttt gcaattgaca taggcaataa taagtgatgtgctgaatttt 3120 ataaataaaa tcatgtagtt tgtgg 3145 31 934 PRT Homo sapiens31 Met Ala Val Gln Pro Lys Glu Thr Leu Gln Leu Glu Ser Ala Ala Glu 1 510 15 Val Gly Phe Val Arg Phe Phe Gln Gly Met Pro Glu Lys Pro Thr Thr 2025 30 Thr Val Arg Leu Phe Asp Arg Gly Asp Phe Tyr Thr Ala His Gly Glu 3540 45 Asp Ala Leu Leu Ala Ala Arg Glu Val Phe Lys Thr Gln Gly Val Ile 5055 60 Lys Tyr Met Gly Pro Ala Gly Ala Lys Asn Leu Gln Ser Val Val Leu 6570 75 80 Ser Lys Met Asn Phe Glu Ser Phe Val Lys Asp Leu Leu Leu Val Arg85 90 95 Gln Tyr Arg Val Glu Val Tyr Lys Asn Arg Ala Gly Asn Lys Ala Ser100 105 110 Lys Glu Asn Asp Trp Tyr Leu Ala Tyr Lys Ala Ser Pro Gly AsnLeu 115 120 125 Ser Gln Phe Glu Asp Ile Leu Phe Gly Asn Asn Asp Met SerAla Ser 130 135 140 Ile Gly Val Val Gly Val Lys Met Ser Ala Val Asp GlyGln Arg Gln 145 150 155 160 Val Gly Val Gly Tyr Val Asp Ser Ile Gln ArgLys Leu Gly Leu Cys 165 170 175 Glu Phe Pro Asp Asn Asp Gln Phe Ser AsnLeu Glu Ala Leu Leu Ile 180 185 190 Gln Ile Gly Pro Lys Glu Cys Val LeuPro Gly Gly Glu Thr Ala Gly 195 200 205 Asp Met Gly Lys Leu Arg Gln IleIle Gln Arg Gly Gly Ile Leu Ile 210 215 220 Thr Glu Arg Lys Lys Ala AspPhe Ser Thr Lys Asp Ile Tyr Gln Asp 225 230 235 240 Leu Asn Arg Leu LeuLys Gly Lys Lys Gly Glu Gln Met Asn Ser Ala 245 250 255 Val Leu Pro GluMet Glu Asn Gln Val Ala Val Ser Ser Leu Ser Ala 260 265 270 Val Ile LysPhe Leu Glu Leu Leu Ser Asp Asp Ser Asn Phe Gly Gln 275 280 285 Phe GluLeu Thr Thr Phe Asp Phe Ser Gln Tyr Met Lys Leu Asp Ile 290 295 300 AlaAla Val Arg Ala Leu Asn Leu Phe Gln Gly Ser Val Glu Asp Thr 305 310 315320 Thr Gly Ser Gln Ser Leu Ala Ala Leu Leu Asn Lys Cys Lys Thr Pro 325330 335 Gln Gly Gln Arg Leu Val Asn Gln Trp Ile Lys Gln Pro Leu Met Asp340 345 350 Lys Asn Arg Ile Glu Glu Arg Leu Asn Leu Val Glu Ala Phe ValGlu 355 360 365 Asp Ala Glu Leu Arg Gln Thr Leu Gln Glu Asp Leu Leu ArgArg Phe 370 375 380 Pro Asp Leu Asn Arg Leu Ala Lys Lys Phe Gln Arg GlnAla Ala Asn 385 390 395 400 Leu Gln Asp Cys Tyr Arg Leu Tyr Gln Gly IleAsn Gln Leu Pro Asn 405 410 415 Val Ile Gln Ala Leu Glu Lys His Glu GlyLys His Gln Lys Leu Leu 420 425 430 Leu Ala Val Phe Val Thr Pro Leu ThrAsp Leu Arg Ser Asp Phe Ser 435 440 445 Lys Phe Gln Glu Met Ile Glu ThrThr Leu Asp Met Asp Gln Val Glu 450 455 460 Asn His Glu Phe Leu Val LysPro Ser Phe Asp Pro Asn Leu Ser Glu 465 470 475 480 Leu Arg Glu Ile MetAsn Asp Leu Glu Lys Lys Met Gln Ser Thr Leu 485 490 495 Ile Ser Ala AlaArg Asp Leu Gly Leu Asp Pro Gly Lys Gln Ile Lys 500 505 510 Leu Asp SerSer Ala Gln Phe Gly Tyr Tyr Phe Arg Val Thr Cys Lys 515 520 525 Glu GluLys Val Leu Arg Asn Asn Lys Asn Phe Ser Thr Val Asp Ile 530 535 540 GlnLys Asn Gly Val Lys Phe Thr Asn Ser Lys Leu Thr Ser Leu Asn 545 550 555560 Glu Glu Tyr Thr Lys Asn Lys Thr Glu Tyr Glu Glu Ala Gln Asp Ala 565570 575 Ile Val Lys Glu Ile Val Asn Ile Ser Ser Gly Tyr Val Glu Pro Met580 585 590 Gln Thr Leu Asn Asp Val Leu Ala Gln Leu Asp Ala Val Val SerPhe 595 600 605 Ala His Val Ser Asn Gly Ala Pro Val Pro Tyr Val Arg ProAla Ile 610 615 620 Leu Glu Lys Gly Gln Gly Arg Ile Ile Leu Lys Ala SerArg His Ala 625 630 635 640 Cys Val Glu Val Gln Asp Glu Ile Ala Phe IlePro Asn Asp Val Tyr 645 650 655 Phe Glu Lys Asp Lys Gln Met Phe His IleIle Thr Gly Pro Asn Met 660 665 670 Gly Gly Lys Ser Thr Tyr Ile Arg GlnThr Gly Val Ile Val Leu Met 675 680 685 Ala Gln Ile Gly Cys Phe Val ProCys Glu Ser Ala Glu Val Ser Ile 690 695 700 Val Asp Cys Ile Leu Ala ArgVal Gly Ala Gly Asp Ser Gln Leu Lys 705 710 715 720 Gly Val Ser Thr PheMet Ala Glu Met Leu Glu Thr Ala Ser Ile Leu 725 730 735 Arg Ser Ala ThrLys Asp Ser Leu Ile Ile Ile Asp Glu Leu Gly Arg 740 745 750 Gly Thr SerThr Tyr Asp Gly Phe Gly Leu Ala Trp Ala Ile Ser Glu 755 760 765 Tyr IleAla Thr Lys Ile Gly Ala Phe Cys Met Phe Ala Thr His Phe 770 775 780 HisGlu Leu Thr Ala Leu Ala Asn Gln Ile Pro Thr Val Asn Asn Leu 785 790 795800 His Val Thr Ala Leu Thr Thr Glu Glu Thr Leu Thr Met Leu Tyr Gln 805810 815 Val Lys Lys Gly Val Cys Asp Gln Ser Phe Gly Ile His Val Ala Glu820 825 830 Leu Ala Asn Phe Pro Lys His Val Ile Glu Cys Ala Lys Gln LysAla 835 840 845 Leu Glu Leu Glu Glu Phe Gln Tyr Ile Gly Glu Ser Gln GlyTyr Asp 850 855 860 Ile Met Glu Pro Ala Ala Lys Lys Cys Tyr Leu Glu ArgGlu Gln Gly 865 870 875 880 Glu Lys Ile Ile Gln Glu Phe Leu Ser Lys ValLys Gln Met Pro Phe 885 890 895 Thr Glu Met Ser Glu Glu Asn Ile Thr IleLys Leu Lys Gln Leu Lys 900 905 910 Ala Glu Val Ile Ala Lys Asn Asn SerPhe Val Asn Glu Ile Ile Ser 915 920 925 Arg Ile Lys Val Thr Thr 930 322484 DNA Homo sapiens 32 cttggctctt ctggcgccaa aatgtcgttc gtggcaggggttattcggcg gctggacgag 60 acagtggtga accgcatcgc ggcgggggaa gttatccagcggccagctaa tgctatcaaa 120 gagatgattg agaactgttt agatgcaaaa tccacaagtattcaagtgat tgttaaagag 180 ggaggcctga agttgattca gatccaagac aatggcaccgggatcaggaa agaagatctg 240 gatattgtat gtgaaaggtt cactactagt aaactgcagtcctttgagga tttagccagt 300 atttctacct atggctttcg aggtgaggct ttggccagcataagccatgt ggctcatgtt 360 actattacaa cgaaaacagc tgatggaaag tgtgcatacagagcaagtta ctcagatgga 420 aaactgaaag cccctcctaa accatgtgct ggcaatcaagggacccagat cacggtggag 480 gacctttttt acaacatagc cacgaggaga aaagctttaaaaaatccaag tgaagaatat 540 gggaaaattt tggaagttgt tggcaggtat tcagtacacaatgcaggcat tagtttctca 600 gttaaaaaac aaggagagac agtagctgat gttaggacactacccaatgc ctcaaccgtg 660 gacaatattc gctccatctt tggaaatgct gttagtcgagaactgataga aattggatgt 720 gaggataaaa ccctagcctt caaaatgaat ggttacatatccaatgcaaa ctactcagtg 780 aagaagtgca tcttcttact cttcatcaac catcgtctggtagaatcaac ttccttgaga 840 aaagccatag aaacagtgta tgcagcctat ttgcccaaaaacacacaccc attcctgtac 900 ctcagtttag aaatcagtcc ccagaatgtg gatgttaatgtgcaccccac aaagcatgaa 960 gttcacttcc tgcacgagga gagcatcctg gagcgggtgcagcagcacat cgagagcaag 1020 ctcctgggct ccaattcctc caggatgtac ttcacccagactttgctacc aggacttgct 1080 ggcccctctg gggagatggt taaatccaca acaagtctgacctcgtcttc tacttctgga 1140 agtagtgata aggtctatgc ccaccagatg gttcgtacagattcccggga acagaagctt 1200 gatgcatttc tgcagcctct gagcaaaccc ctgtccagtcagccccaggc cattgtcaca 1260 gaggataaga cagatatttc tagtggcagg gctaggcagcaagatgagga gatgcttgaa 1320 ctcccagccc ctgctgaagt ggctgccaaa aatcagagcttggaggggga tacaacaaag 1380 gggacttcag aaatgtcaga gaagagagga cctacttccagcaaccccag aaagagacat 1440 cgggaagatt ctgatgtgga aatggtggaa gatgattcccgaaaggaaat gactgcagct 1500 tgtacccccc ggagaaggat cattaacctc actagtgttttgagtctcca ggaagaaatt 1560 aatgagcagg gacatgaggt tctccgggag atgttgcataaccactcctt cgtgggctgt 1620 gtgaatcctc agtgggcctt ggcacagcat caaaccaagttataccttct caacaccacc 1680 aagcttagtg aagaactgtt ctaccagata ctcatttatgattttgccaa ttttggtgtt 1740 ctcaggttat cggagccagc accgctcttt gaccttgccatgcttgcctt agatagtcca 1800 gagagtggct ggacagagga agatggtccc aaagaaggacttgctgaata cattgttgag 1860 tttctgaaga agaaggctga gatgcttgca gactatttctctttggaaat tgatgaggaa 1920 gggaacctga ttggattacc ccttctgatt gacaactatgtgcccccttt ggagggactg 1980 cctatcttca ttcttcgact agccactgag gtgaattgggacgaagaaaa ggaatgtttt 2040 gaaagcctca gtaaagaatg cgctatgttc tattccatccggaagcagta catatctgag 2100 gagtcgaccc tctcaggcca gcagagtgaa gtgcctggctccattccaaa ctcctggaag 2160 tggactgtgg aacacattgt ctataaagcc ttgcgctcacacattctgcc tcctaaacat 2220 ttcacagaag atggaaatat cctgcagctt gctaacctgcctgatctata caaagtcttt 2280 gagaggtgtt aaatatggtt atttatgcac tgtgggatgtgttcttcttt ctctgtattc 2340 cgatacaaag tgttgtatca aagtgtgata tacaaagtgtaccaacataa gtgttggtag 2400 cacttaagac ttatacttgc cttctgatag tattcctttatacacagtgg attgattata 2460 aataaataga tgtgtcttaa cata 2484 33 756 PRTHomo sapiens 33 Met Ser Phe Val Ala Gly Val Ile Arg Arg Leu Asp Glu ThrVal Val 1 5 10 15 Asn Arg Ile Ala Ala Gly Glu Val Ile Gln Arg Pro AlaAsn Ala Ile 20 25 30 Lys Glu Met Ile Glu Asn Cys Leu Asp Ala Lys Ser ThrSer Ile Gln 35 40 45 Val Ile Val Lys Glu Gly Gly Leu Lys Leu Ile Gln IleGln Asp Asn 50 55 60 Gly Thr Gly Ile Arg Lys Glu Asp Leu Asp Ile Val CysGlu Arg Phe 65 70 75 80 Thr Thr Ser Lys Leu Gln Ser Phe Glu Asp Leu AlaSer Ile Ser Thr 85 90 95 Tyr Gly Phe Arg Gly Glu Ala Leu Ala Ser Ile SerHis Val Ala His 100 105 110 Val Thr Ile Thr Thr Lys Thr Ala Asp Gly LysCys Ala Tyr Arg Ala 115 120 125 Ser Tyr Ser Asp Gly Lys Leu Lys Ala ProPro Lys Pro Cys Ala Gly 130 135 140 Asn Gln Gly Thr Gln Ile Thr Val GluAsp Leu Phe Tyr Asn Ile Ala 145 150 155 160 Thr Arg Arg Lys Ala Leu LysAsn Pro Ser Glu Glu Tyr Gly Lys Ile 165 170 175 Leu Glu Val Val Gly ArgTyr Ser Val His Asn Ala Gly Ile Ser Phe 180 185 190 Ser Val Lys Lys GlnGly Glu Thr Val Ala Asp Val Arg Thr Leu Pro 195 200 205 Asn Ala Ser ThrVal Asp Asn Ile Arg Ser Ile Phe Gly Asn Ala Val 210 215 220 Ser Arg GluLeu Ile Glu Ile Gly Cys Glu Asp Lys Thr Leu Ala Phe 225 230 235 240 LysMet Asn Gly Tyr Ile Ser Asn Ala Asn Tyr Ser Val Lys Lys Cys 245 250 255Ile Phe Leu Leu Phe Ile Asn His Arg Leu Val Glu Ser Thr Ser Leu 260 265270 Arg Lys Ala Ile Glu Thr Val Tyr Ala Ala Tyr Leu Pro Lys Asn Thr 275280 285 His Pro Phe Leu Tyr Leu Ser Leu Glu Ile Ser Pro Gln Asn Val Asp290 295 300 Val Asn Val His Pro Thr Lys His Glu Val His Phe Leu His GluGlu 305 310 315 320 Ser Ile Leu Glu Arg Val Gln Gln His Ile Glu Ser LysLeu Leu Gly 325 330 335 Ser Asn Ser Ser Arg Met Tyr Phe Thr Gln Thr LeuLeu Pro Gly Leu 340 345 350 Ala Gly Pro Ser Gly Glu Met Val Lys Ser ThrThr Ser Leu Thr Ser 355 360 365 Ser Ser Thr Ser Gly Ser Ser Asp Lys ValTyr Ala His Gln Met Val 370 375 380 Arg Thr Asp Ser Arg Glu Gln Lys LeuAsp Ala Phe Leu Gln Pro Leu 385 390 395 400 Ser Lys Pro Leu Ser Ser GlnPro Gln Ala Ile Val Thr Glu Asp Lys 405 410 415 Thr Asp Ile Ser Ser GlyArg Ala Arg Gln Gln Asp Glu Glu Met Leu 420 425 430 Glu Leu Pro Ala ProAla Glu Val Ala Ala Lys Asn Gln Ser Leu Glu 435 440 445 Gly Asp Thr ThrLys Gly Thr Ser Glu Met Ser Glu Lys Arg Gly Pro 450 455 460 Thr Ser SerAsn Pro Arg Lys Arg His Arg Glu Asp Ser Asp Val Glu 465 470 475 480 MetVal Glu Asp Asp Ser Arg Lys Glu Met Thr Ala Ala Cys Thr Pro 485 490 495Arg Arg Arg Ile Ile Asn Leu Thr Ser Val Leu Ser Leu Gln Glu Glu 500 505510 Ile Asn Glu Gln Gly His Glu Val Leu Arg Glu Met Leu His Asn His 515520 525 Ser Phe Val Gly Cys Val Asn Pro Gln Trp Ala Leu Ala Gln His Gln530 535 540 Thr Lys Leu Tyr Leu Leu Asn Thr Thr Lys Leu Ser Glu Glu LeuPhe 545 550 555 560 Tyr Gln Ile Leu Ile Tyr Asp Phe Ala Asn Phe Gly ValLeu Arg Leu 565 570 575 Ser Glu Pro Ala Pro Leu Phe Asp Leu Ala Met LeuAla Leu Asp Ser 580 585 590 Pro Glu Ser Gly Trp Thr Glu Glu Asp Gly ProLys Glu Gly Leu Ala 595 600 605 Glu Tyr Ile Val Glu Phe Leu Lys Lys LysAla Glu Met Leu Ala Asp 610 615 620 Tyr Phe Ser Leu Glu Ile Asp Glu GluGly Asn Leu Ile Gly Leu Pro 625 630 635 640 Leu Leu Ile Asp Asn Tyr ValPro Pro Leu Glu Gly Leu Pro Ile Phe 645 650 655 Ile Leu Arg Leu Ala ThrGlu Val Asn Trp Asp Glu Glu Lys Glu Cys 660 665 670 Phe Glu Ser Leu SerLys Glu Cys Ala Met Phe Tyr Ser Ile Arg Lys 675 680 685 Gln Tyr Ile SerGlu Glu Ser Thr Leu Ser Gly Gln Gln Ser Glu Val 690 695 700 Pro Gly SerIle Pro Asn Ser Trp Lys Trp Thr Val Glu His Ile Val 705 710 715 720 TyrLys Ala Leu Arg Ser His Ile Leu Pro Pro Lys His Phe Thr Glu 725 730 735Asp Gly Asn Ile Leu Gln Leu Ala Asn Leu Pro Asp Leu Tyr Lys Val 740 745750 Phe Glu Arg Cys 755 34 426 DNA Homo sapiens 34 cgaggcggat cgggtgttgcatccatggag cgagctgaga gctcgagtac agaacctgct 60 aaggccatca aacctattgatcggaagtca gtccatcaga tttgctctgg gcaggtggta 120 ctgagtctaa gcactgcggtaaaggagtta gtagaaaaca gtctggatgc tggtgccact 180 aatattgatc taaagcttaaggactatgga gtggatctta ttgaagtttc agacaatgga 240 tgtggggtag aagaagaaaacttcgaaggc ttaactctga aacatcacac atctaagatt 300 caagagtttg ccgacctaactcaggttgaa acttttggct ttcgggggga agctctgagc 360 tcactttgtg cactgagcgatgtcaccatt tctacctgcc acgcatcggc gaaggttgga 420 acttga 426 35 133 PRTHomo sapiens 35 Met Lys Gln Leu Pro Ala Ala Thr Val Arg Leu Leu Ser SerSer Gln 1 5 10 15 Ile Ile Thr Ser Val Val Ser Val Val Lys Glu Leu IleGlu Asn Ser 20 25 30 Leu Asp Ala Gly Ala Thr Ser Val Asp Val Lys Leu GluAsn Tyr Gly 35 40 45 Phe Asp Lys Ile Glu Val Arg Asp Asn Gly Glu Gly IleLys Ala Val 50 55 60 Asp Ala Pro Val Met Ala Met Lys Tyr Tyr Thr Ser LysIle Asn Ser 65 70 75 80 His Glu Asp Leu Glu Asn Leu Thr Thr Tyr Gly PheArg Gly Glu Ala 85 90 95 Leu Gly Ser Ile Cys Cys Ile Ala Glu Val Leu IleThr Thr Arg Thr 100 105 110 Ala Ala Asp Asn Phe Ser Thr Gln Tyr Val LeuAsp Gly Ser Gly His 115 120 125 Ile Leu Ser Gln Lys 130 36 4264 DNA Homosapiens 36 atttcccgcc agcaggagcc gcgcggtaga tgcggtgctt ttaggagctccgtccgacag 60 aacggttggg ccttgccggc tgtcggtatg tcgcgacaga gcaccctgtacagcttcttc 120 cccaagtctc cggcgctgag tgatgccaac aaggcctcgg ccagggcctcacgcgaaggc 180 ggccgtgccg ccgctgcccc cggggcctct ccttccccag gcggggatgcggcctggagc 240 gaggctgggc ctgggcccag gcccttggcg cgatccgcgt caccgcccaaggcgaagaac 300 ctcaacggag ggctgcggag atcggtagcg cctgctgccc ccaccagttgtgacttctca 360 ccaggagatt tggtttgggc caagatggag ggttacccct ggtggccttgtctggtttac 420 aaccacccct ttgatggaac attcatccgc gagaaaggga aatcagtccgtgttcatgta 480 cagttttttg atgacagccc aacaaggggc tgggttagca aaaggcttttaaagccatat 540 acaggttcaa aatcaaagga agcccagaag ggaggtcatt tttacagtgcaaagcctgaa 600 atactgagag caatgcaacg tgcagatgaa gccttaaata aagacaagattaagaggctt 660 gaattggcag tttgtgatga gccctcagag ccagaagagg aagaagagatggaggtaggc 720 acaacttacg taacagataa gagtgaagaa gataatgaaa ttgagagtgaagaggaagta 780 cagcctaaga cacaaggatc taggcgaagt agccgccaaa taaaaaaacgaagggtcata 840 tcagattctg agagtgacat tggtggctct gatgtggaat ttaagccagacactaaggag 900 gaaggaagca gtgatgaaat aagcagtgga gtgggggata gtgagagtgaaggcctgaac 960 agccctgtca aagttgctcg aaagcggaag agaatggtga ctggaaatggctctcttaaa 1020 aggaaaagct ctaggaagga aacgccctca gccaccaaac aagcaactagcatttcatca 1080 gaaaccaaga atactttgag agctttctct gcccctcaaa attctgaatcccaagcccac 1140 gttagtggag gtggtgatga cagtagtcgc cctactgttt ggtatcatgaaactttagaa 1200 tggcttaagg aggaaaagag aagagatgag cacaggagga ggcctgatcaccccgatttt 1260 gatgcatcta cactctatgt gcctgaggat ttcctcaatt cttgtactcctgggatgagg 1320 aagtggtggc agattaagtc tcagaacttt gatcttgtca tctgttacaaggtggggaaa 1380 ttttatgagc tgtaccacat ggatgctctt attggagtca gtgaactggggctggtattc 1440 atgaaaggca actgggccca ttctggcttt cctgaaattg catttggccgttattcagat 1500 tccctggtgc agaagggcta taaagtagca cgagtggaac agactgagactccagaaatg 1560 atggaggcac gatgtagaaa gatggcacat atatccaagt atgatagagtggtgaggagg 1620 gagatctgta ggatcattac caagggtaca cagacttaca gtgtgctggaaggtgatccc 1680 tctgagaact acagtaagta tcttcttagc ctcaaagaaa aagaggaagattcttctggc 1740 catactcgtg catatggtgt gtgctttgtt gatacttcac tgggaaagtttttcataggt 1800 cagttttcag atgatcgcca ttgttcgaga tttaggactc tagtggcacactatccccca 1860 gtacaagttt tatttgaaaa aggaaatctc tcaaaggaaa ctaaaacaattctaaagagt 1920 tcattgtcct gttctcttca ggaaggtctg atacccggct cccagttttgggatgcatcc 1980 aaaactttga gaactctcct tgaggaagaa tattttaggg aaaagctaagtgatggcatt 2040 ggggtgatgt taccccaggt gcttaaaggt atgacttcag agtctgattccattgggttg 2100 acaccaggag agaaaagtga attggccctc tctgctctag gtggttgtgtcttctacctc 2160 aaaaaatgcc ttattgatca ggagctttta tcaatggcta attttgaagaatatattccc 2220 ttggattctg acacagtcag cactacaaga tctggtgcta tcttcaccaaagcctatcaa 2280 cgaatggtgc tagatgcagt gacattaaac aacttggaga tttttctgaatggaacaaat 2340 ggttctactg aaggaaccct actagagagg gttgatactt gccatactccttttggtaag 2400 cggctcctaa agcaatggct ttgtgcccca ctctgtaacc attatgctattaatgatcgt 2460 ctagatgcca tagaagacct catggttgtg cctgacaaaa tctccgaagttgtagagctt 2520 ctaaagaagc ttccagatct tgagaggcta ctcagtaaaa ttcataatgttgggtctccc 2580 ctgaagagtc agaaccaccc agacagcagg gctataatgt atgaagaaactacatacagc 2640 aagaagaaga ttattgattt tctttctgct ctggaaggat tcaaagtaatgtgtaaaatt 2700 atagggatca tggaagaagt tgctgatggt tttaagtcta aaatccttaagcaggtcatc 2760 tctctgcaga caaaaaatcc tgaaggtcgt tttcctgatt tgactgtagaattgaaccga 2820 tgggatacag cctttgacca tgaaaaggct cgaaagactg gacttattactcccaaagca 2880 ggctttgact ctgattatga ccaagctctt gctgacataa gagaaaatgaacagagcctc 2940 ctggaatacc tagagaaaca gcgcaacaga attggctgta ggaccatagtctattggggg 3000 attggtagga accgttacca gctggaaatt cctgagaatt tcaccactcgcaatttgcca 3060 gaagaatacg agttgaaatc taccaagaag ggctgtaaac gatactggaccaaaactatt 3120 gaaaagaagt tggctaatct cataaatgct gaagaacgga gggatgtatcattgaaggac 3180 tgcatgcggc gactgttcta taactttgat aaaaattaca aggactggcagtctgctgta 3240 gagtgtatcg cagtgttgga tgttttactg tgcctggcta actatagtcgagggggtgat 3300 ggtcctatgt gtcgcccagt aattctgttg ccggaagata ccccccccttcttagagctt 3360 aaaggatcac gccatccttg cattacgaag actttttttg gagatgattttattcctaat 3420 gacattctaa taggctgtga ggaagaggag caggaaaatg gcaaagcctattgtgtgctt 3480 gttactggac caaatatggg gggcaagtct acgcttatga gacaggctggcttattagct 3540 gtaatggccc agatgggttg ttacgtccct gctgaagtgt gcaggctcacaccaattgat 3600 agagtgttta ctagacttgg tgcctcagac agaataatgt caggtgaaagtacatttttt 3660 gttgaattaa gtgaaactgc cagcatactc atgcatgcaa cagcacattctctggtgctt 3720 gtggatgaat taggaagagg tactgcaaca tttgatggga cggcaatagcaaatgcagtt 3780 gttaaagaac ttgctgagac tataaaatgt cgtacattat tttcaactcactaccattca 3840 ttagtagaag attattctca aaatgttgct gtgcgcctag gacatatggcatgcatggta 3900 gaaaatgaat gtgaagaccc cagccaggag actattacgt tcctctataaattcattaag 3960 ggagcttgtc ctaaaagcta tggctttaat gcagcaaggc ttgctaatctcccagaggaa 4020 gttattcaaa agggacatag aaaagcaaga gaatttgaga agatgaatcagtcactacga 4080 ttatttcggg aagtttgcct ggctagtgaa aggtcaactg tagatgctgaagctgtccat 4140 aaattgctga ctttgattaa ggaattatag actgactaca ttggaagctttgagttgact 4200 tctgaccaaa ggtggtaaat tcagacaaca ttatgatcta ataaactttattttttaaaa 4260 atga 4264 37 1360 PRT Homo sapiens 37 Met Ser Arg GlnSer Thr Leu Tyr Ser Phe Phe Pro Lys Ser Pro Ala 1 5 10 15 Leu Ser AspAla Asn Lys Ala Ser Ala Arg Ala Ser Arg Glu Gly Gly 20 25 30 Arg Ala AlaAla Ala Pro Gly Ala Ser Pro Ser Pro Gly Gly Asp Ala 35 40 45 Ala Trp SerGlu Ala Gly Pro Gly Pro Arg Pro Leu Ala Arg Ser Ala 50 55 60 Ser Pro ProLys Ala Lys Asn Leu Asn Gly Gly Leu Arg Arg Ser Val 65 70 75 80 Ala ProAla Ala Pro Thr Ser Cys Asp Phe Ser Pro Gly Asp Leu Val 85 90 95 Trp AlaLys Met Glu Gly Tyr Pro Trp Trp Pro Cys Leu Val Tyr Asn 100 105 110 HisPro Phe Asp Gly Thr Phe Ile Arg Glu Lys Gly Lys Ser Val Arg 115 120 125Val His Val Gln Phe Phe Asp Asp Ser Pro Thr Arg Gly Trp Val Ser 130 135140 Lys Arg Leu Leu Lys Pro Tyr Thr Gly Ser Lys Ser Lys Glu Ala Gln 145150 155 160 Lys Gly Gly His Phe Tyr Ser Ala Lys Pro Glu Ile Leu Arg AlaMet 165 170 175 Gln Arg Ala Asp Glu Ala Leu Asn Lys Asp Lys Ile Lys ArgLeu Glu 180 185 190 Leu Ala Val Cys Asp Glu Pro Ser Glu Pro Glu Glu GluGlu Glu Met 195 200 205 Glu Val Gly Thr Thr Tyr Val Thr Asp Lys Ser GluGlu Asp Asn Glu 210 215 220 Ile Glu Ser Glu Glu Glu Val Gln Pro Lys ThrGln Gly Ser Arg Arg 225 230 235 240 Ser Ser Arg Gln Ile Lys Lys Arg ArgVal Ile Ser Asp Ser Glu Ser 245 250 255 Asp Ile Gly Gly Ser Asp Val GluPhe Lys Pro Asp Thr Lys Glu Glu 260 265 270 Gly Ser Ser Asp Glu Ile SerSer Gly Val Gly Asp Ser Glu Ser Glu 275 280 285 Gly Leu Asn Ser Pro ValLys Val Ala Arg Lys Arg Lys Arg Met Val 290 295 300 Thr Gly Asn Gly SerLeu Lys Arg Lys Ser Ser Arg Lys Glu Thr Pro 305 310 315 320 Ser Ala ThrLys Gln Ala Thr Ser Ile Ser Ser Glu Thr Lys Asn Thr 325 330 335 Leu ArgAla Phe Ser Ala Pro Gln Asn Ser Glu Ser Gln Ala His Val 340 345 350 SerGly Gly Gly Asp Asp Ser Ser Arg Pro Thr Val Trp Tyr His Glu 355 360 365Thr Leu Glu Trp Leu Lys Glu Glu Lys Arg Arg Asp Glu His Arg Arg 370 375380 Arg Pro Asp His Pro Asp Phe Asp Ala Ser Thr Leu Tyr Val Pro Glu 385390 395 400 Asp Phe Leu Asn Ser Cys Thr Pro Gly Met Arg Lys Trp Trp GlnIle 405 410 415 Lys Ser Gln Asn Phe Asp Leu Val Ile Cys Tyr Lys Val GlyLys Phe 420 425 430 Tyr Glu Leu Tyr His Met Asp Ala Leu Ile Gly Val SerGlu Leu Gly 435 440 445 Leu Val Phe Met Lys Gly Asn Trp Ala His Ser GlyPhe Pro Glu Ile 450 455 460 Ala Phe Gly Arg Tyr Ser Asp Ser Leu Val GlnLys Gly Tyr Lys Val 465 470 475 480 Ala Arg Val Glu Gln Thr Glu Thr ProGlu Met Met Glu Ala Arg Cys 485 490 495 Arg Lys Met Ala His Ile Ser LysTyr Asp Arg Val Val Arg Arg Glu 500 505 510 Ile Cys Arg Ile Ile Thr LysGly Thr Gln Thr Tyr Ser Val Leu Glu 515 520 525 Gly Asp Pro Ser Glu AsnTyr Ser Lys Tyr Leu Leu Ser Leu Lys Glu 530 535 540 Lys Glu Glu Asp SerSer Gly His Thr Arg Ala Tyr Gly Val Cys Phe 545 550 555 560 Val Asp ThrSer Leu Gly Lys Phe Phe Ile Gly Gln Phe Ser Asp Asp 565 570 575 Arg HisCys Ser Arg Phe Arg Thr Leu Val Ala His Tyr Pro Pro Val 580 585 590 GlnVal Leu Phe Glu Lys Gly Asn Leu Ser Lys Glu Thr Lys Thr Ile 595 600 605Leu Lys Ser Ser Leu Ser Cys Ser Leu Gln Glu Gly Leu Ile Pro Gly 610 615620 Ser Gln Phe Trp Asp Ala Ser Lys Thr Leu Arg Thr Leu Leu Glu Glu 625630 635 640 Glu Tyr Phe Arg Glu Lys Leu Ser Asp Gly Ile Gly Val Met LeuPro 645 650 655 Gln Val Leu Lys Gly Met Thr Ser Glu Ser Asp Ser Ile GlyLeu Thr 660 665 670 Pro Gly Glu Lys Ser Glu Leu Ala Leu Ser Ala Leu GlyGly Cys Val 675 680 685 Phe Tyr Leu Lys Lys Cys Leu Ile Asp Gln Glu LeuLeu Ser Met Ala 690 695 700 Asn Phe Glu Glu Tyr Ile Pro Leu Asp Ser AspThr Val Ser Thr Thr 705 710 715 720 Arg Ser Gly Ala Ile Phe Thr Lys AlaTyr Gln Arg Met Val Leu Asp 725 730 735 Ala Val Thr Leu Asn Asn Leu GluIle Phe Leu Asn Gly Thr Asn Gly 740 745 750 Ser Thr Glu Gly Thr Leu LeuGlu Arg Val Asp Thr Cys His Thr Pro 755 760 765 Phe Gly Lys Arg Leu LeuLys Gln Trp Leu Cys Ala Pro Leu Cys Asn 770 775 780 His Tyr Ala Ile AsnAsp Arg Leu Asp Ala Ile Glu Asp Leu Met Val 785 790 795 800 Val Pro AspLys Ile Ser Glu Val Val Glu Leu Leu Lys Lys Leu Pro 805 810 815 Asp LeuGlu Arg Leu Leu Ser Lys Ile His Asn Val Gly Ser Pro Leu 820 825 830 LysSer Gln Asn His Pro Asp Ser Arg Ala Ile Met Tyr Glu Glu Thr 835 840 845Thr Tyr Ser Lys Lys Lys Ile Ile Asp Phe Leu Ser Ala Leu Glu Gly 850 855860 Phe Lys Val Met Cys Lys Ile Ile Gly Ile Met Glu Glu Val Ala Asp 865870 875 880 Gly Phe Lys Ser Lys Ile Leu Lys Gln Val Ile Ser Leu Gln ThrLys 885 890 895 Asn Pro Glu Gly Arg Phe Pro Asp Leu Thr Val Glu Leu AsnArg Trp 900 905 910 Asp Thr Ala Phe Asp His Glu Lys Ala Arg Lys Thr GlyLeu Ile Thr 915 920 925 Pro Lys Ala Gly Phe Asp Ser Asp Tyr Asp Gln AlaLeu Ala Asp Ile 930 935 940 Arg Glu Asn Glu Gln Ser Leu Leu Glu Tyr LeuGlu Lys Gln Arg Asn 945 950 955 960 Arg Ile Gly Cys Arg Thr Ile Val TyrTrp Gly Ile Gly Arg Asn Arg 965 970 975 Tyr Gln Leu Glu Ile Pro Glu AsnPhe Thr Thr Arg Asn Leu Pro Glu 980 985 990 Glu Tyr Glu Leu Lys Ser ThrLys Lys Gly Cys Lys Arg Tyr Trp Thr 995 1000 1005 Lys Thr Ile Glu LysLys Leu Ala Asn Leu Ile Asn Ala Glu Glu 1010 1015 1020 Arg Arg Asp ValSer Leu Lys Asp Cys Met Arg Arg Leu Phe Tyr 1025 1030 1035 Asn Phe AspLys Asn Tyr Lys Asp Trp Gln Ser Ala Val Glu Cys 1040 1045 1050 Ile AlaVal Leu Asp Val Leu Leu Cys Leu Ala Asn Tyr Ser Arg 1055 1060 1065 GlyGly Asp Gly Pro Met Cys Arg Pro Val Ile Leu Leu Pro Glu 1070 1075 1080Asp Thr Pro Pro Phe Leu Glu Leu Lys Gly Ser Arg His Pro Cys 1085 10901095 Ile Thr Lys Thr Phe Phe Gly Asp Asp Phe Ile Pro Asn Asp Ile 11001105 1110 Leu Ile Gly Cys Glu Glu Glu Glu Gln Glu Asn Gly Lys Ala Tyr1115 1120 1125 Cys Val Leu Val Thr Gly Pro Asn Met Gly Gly Lys Ser ThrLeu 1130 1135 1140 Met Arg Gln Ala Gly Leu Leu Ala Val Met Ala Gln MetGly Cys 1145 1150 1155 Tyr Val Pro Ala Glu Val Cys Arg Leu Thr Pro IleAsp Arg Val 1160 1165 1170 Phe Thr Arg Leu Gly Ala Ser Asp Arg Ile MetSer Gly Glu Ser 1175 1180 1185 Thr Phe Phe Val Glu Leu Ser Glu Thr AlaSer Ile Leu Met His 1190 1195 1200 Ala Thr Ala His Ser Leu Val Leu ValAsp Glu Leu Gly Arg Gly 1205 1210 1215 Thr Ala Thr Phe Asp Gly Thr AlaIle Ala Asn Ala Val Val Lys 1220 1225 1230 Glu Leu Ala Glu Thr Ile LysCys Arg Thr Leu Phe Ser Thr His 1235 1240 1245 Tyr His Ser Leu Val GluAsp Tyr Ser Gln Asn Val Ala Val Arg 1250 1255 1260 Leu Gly His Met AlaCys Met Val Glu Asn Glu Cys Glu Asp Pro 1265 1270 1275 Ser Gln Glu ThrIle Thr Phe Leu Tyr Lys Phe Ile Lys Gly Ala 1280 1285 1290 Cys Pro LysSer Tyr Gly Phe Asn Ala Ala Arg Leu Ala Asn Leu 1295 1300 1305 Pro GluGlu Val Ile Gln Lys Gly His Arg Lys Ala Arg Glu Phe 1310 1315 1320 GluLys Met Asn Gln Ser Leu Arg Leu Phe Arg Glu Val Cys Leu 1325 1330 1335Ala Ser Glu Arg Ser Thr Val Asp Ala Glu Ala Val His Lys Leu 1340 13451350 Leu Thr Leu Ile Lys Glu Leu 1355 1360 38 1408 DNA Homo sapiens 38ggcgctccta cctgcaagtg gctagtgcca agtgctgggc cgccgctcct gccgtgcatg 60ttggggagcc agtacatgca ggtgggctcc acacggagag gggcgcagac ccggtgacag 120ggctttacct ggtacatcgg catggcgcaa ccaaagcaag agagggtggc gcgtgccaga 180caccaacggt cggaaaccgc cagacaccaa cggtcggaaa ccgccaagac accaacgctc 240ggaaaccgcc agacaccaac gctcggaaac cgccagacac caaggctcgg aatccacgcc 300aggccacgac ggagggcgac tacctccctt ctgaccctgc tgctggcgtt cggaaaaaac 360gcagtccggt gtgctctgat tggtccaggc tctttgacgt cacggactcg acctttgaca 420gagccactag gcgaaaagga gagacgggaa gtattttttc cgccccgccc ggaaagggtg 480gagcacaacg tcgaaagcag ccgttgggag cccaggaggc ggggcgcctg tgggagccgt 540ggagggaact ttcccagtcc ccgaggcgga tccggtgttg catccttgga gcgagctgag 600aactcgagta cagaacctgc taaggccatc aaacctattg atcggaagtc agtccatcag 660atttgctctg ggccggtggt accgagtcta aggccgaatg cggtgaagga gttagtagaa 720aacagtctgg atgctggtgc cactaatgtt gatctaaagc ttaaggacta tggagtggat 780ctcattgaag tttcaggcaa tggatgtggg gtagaagaag aaaacttcga aggctttact 840ctgaaacatc acacatgtaa gattcaagag tttgccgacc taactcaggt ggaaactttt 900ggctttcggg gggaagctct gagctcactt tgtgcactga gtgatgtcac catttctacc 960tgccgtgtat cagcgaaggt tgggactcga ctggtgtttg atcactatgg gaaaatcatc 1020cagaaaaccc cctacccccg ccccagaggg atgacagtca gcgtgaagca gttattttct 1080acgctacctg tgcaccataa agaatttcaa aggaatatta agaagaaacg tgcctgcttc 1140cccttcgcct tctgccgtga ttgtcagttt cctgaggcct ccccagccat gcttcctgta 1200cagcctgtag aactgactcc tagaagtacc ccaccccacc cctgctcctt ggaggacaac 1260gtgatcactg tattcagctc tgtcaagaat ggtccaggtt cttctagatg atctgcacaa 1320atggttcctc tcctccttcc tgatgtctgc cattagcatt ggaataaagt tcctgctgaa 1380aatccaaaaa aaaaaaaaaa aaaaaaaa 1408 39 389 PRT Homo sapiens 39 Met AlaGln Pro Lys Gln Glu Arg Val Ala Arg Ala Arg His Gln Arg 1 5 10 15 SerGlu Thr Ala Arg His Gln Arg Ser Glu Thr Ala Lys Thr Pro Thr 20 25 30 LeuGly Asn Arg Gln Thr Pro Thr Leu Gly Asn Arg Gln Thr Pro Arg 35 40 45 LeuGly Ile His Ala Arg Pro Arg Arg Arg Ala Thr Thr Ser Leu Leu 50 55 60 ThrLeu Leu Leu Ala Phe Gly Lys Asn Ala Val Arg Cys Ala Leu Ile 65 70 75 80Gly Pro Gly Ser Leu Thr Ser Arg Thr Arg Pro Leu Thr Glu Pro Leu 85 90 95Gly Glu Lys Glu Arg Arg Glu Val Phe Phe Pro Pro Arg Pro Glu Arg 100 105110 Val Glu His Asn Val Glu Ser Ser Arg Trp Glu Pro Arg Arg Arg Gly 115120 125 Ala Cys Gly Ser Arg Gly Gly Asn Phe Pro Ser Pro Arg Gly Gly Ser130 135 140 Gly Val Ala Ser Leu Glu Arg Ala Glu Asn Ser Ser Thr Glu ProAla 145 150 155 160 Lys Ala Ile Lys Pro Ile Asp Arg Lys Ser Val His GlnIle Cys Ser 165 170 175 Gly Pro Val Val Pro Ser Leu Arg Pro Asn Ala ValLys Glu Leu Val 180 185 190 Glu Asn Ser Leu Asp Ala Gly Ala Thr Asn ValAsp Leu Lys Leu Lys 195 200 205 Asp Tyr Gly Val Asp Leu Ile Glu Val SerGly Asn Gly Cys Gly Val 210 215 220 Glu Glu Glu Asn Phe Glu Gly Phe ThrLeu Lys His His Thr Cys Lys 225 230 235 240 Ile Gln Glu Phe Ala Asp LeuThr Gln Val Glu Thr Phe Gly Phe Arg 245 250 255 Gly Glu Ala Leu Ser SerLeu Cys Ala Leu Ser Asp Val Thr Ile Ser 260 265 270 Thr Cys Arg Val SerAla Lys Val Gly Thr Arg Leu Val Phe Asp His 275 280 285 Tyr Gly Lys IleIle Gln Lys Thr Pro Tyr Pro Arg Pro Arg Gly Met 290 295 300 Thr Val SerVal Lys Gln Leu Phe Ser Thr Leu Pro Val His His Lys 305 310 315 320 GluPhe Gln Arg Asn Ile Lys Lys Lys Arg Ala Cys Phe Pro Phe Ala 325 330 335Phe Cys Arg Asp Cys Gln Phe Pro Glu Ala Ser Pro Ala Met Leu Pro 340 345350 Val Gln Pro Val Glu Leu Thr Pro Arg Ser Thr Pro Pro His Pro Cys 355360 365 Ser Leu Glu Asp Asn Val Ile Thr Val Phe Ser Ser Val Lys Asn Gly370 375 380 Pro Gly Ser Ser Arg 385 40 1785 DNA Homo sapiens 40tttttagaaa ctgatgttta ttttccatca accatttttc catgctgctt aagagaatat 60gcaagaacag cttaagacca gtcagtggtt gctcctaccc attcagtggc ctgagcagtg 120gggagctgca gaccagtctt ccgtggcagg ctgagcgctc cagtcttcag tagggaattg 180ctgaataggc acagagggca cctgtacacc ttcagaccag tctgcaacct caggctgagt 240agcagtgaac tcaggagcgg gagcagtcca ttcaccctga aattcctcct tggtcactgc 300cttctcagca gcagcctgct cttctttttc aatctcttca ggatctctgt agaagtacag 360atcaggcatg acctcccatg ggtgttcacg ggaaatggtg ccacgcatgc gcagaacttc 420ccgagccagc atccaccaca ttaaacccac tgagtgagct cccttgttgt tgcatgggat 480ggcaatgtcc acatagcgca gaggagaatc tgtgttacac agcgcaatgg taggtaggtt 540aacataagat gcctccgtga gaggcgaagg ggcggcggga cccgggcctg gcccgtatgt 600gtccttggcg gcctagacta ggccgtcgct gtatggtgag ccccagggag gcggatctgg 660gcccccagaa ggacacccgc ctggatttgc cccgtagccc ggcccgggcc cctcgggagc 720agaacagcct tggtgaggtg gacaggaggg gacctcgcga gcagacgcgc gcgccagcga 780cagcagcccc gccccggcct ctcgggagcc ggggggcaga ggctgcggag ccccaggagg 840gtctatcagc cacagtctct gcatgtttcc aagagcaaca ggaaatgaac acattgcagg 900ggccagtgtc attcaaagat gtggctgtgg atttcaccca ggaggagtgg cggcaactgg 960accctgatga gaagatagca tacggggatg tgatgttgga gaactacagc catctagttt 1020ctgtggggta tgattatcac caagccaaac atcatcatgg agtggaggtg aaggaagtgg 1080agcagggaga ggagccgtgg ataatggaag gtgaatttcc atgtcaacat agtccagaac 1140ctgctaaggc catcaaacct attgatcgga agtcagtcca tcagatttgc tctgggccag 1200tggtactgag tctaagcact gcagtgaagg agttagtaga aaacagtctg gatgctggtg 1260ccactaatat tgatctaaag cttaaggact atggagtgga tctcattgaa gtttcagaca 1320atggatgtgg ggtagaagaa gaaaactttg aaggcttaat ctctttcagc tctgaaacat 1380cacacatgta agattcaaga gtttgccgac ctaactgaag ttgaaacttt cggttttcag 1440ggggaagctc tgagctcact gtgtgcactg agcgatgtca ccatttctac ctgccacgcg 1500ttggtgaagg ttgggactcg actggtgttt gatcacgatg ggaaaatcat ccaggaaacc 1560ccctaccccc accccagagg gaccacagtc agcgtgaagc agttattttc tacgctacct 1620gtgcgccata aggaatttca aaggaatatt aagaagacgt gcctgcttcc ccttcgcctt 1680ctgccgtgat tgtcagtttc ctgaggcctc cccagccatg cttcctgtac agcctgcaga 1740actgtgagtc aattaaacct cttttcttca taaattaaaa aaaaa 1785 41 264 PRT Homosapiens 41 Met Cys Pro Trp Arg Pro Arg Leu Gly Arg Arg Cys Met Val SerPro 1 5 10 15 Arg Glu Ala Asp Leu Gly Pro Gln Lys Asp Thr Arg Leu AspLeu Pro 20 25 30 Arg Ser Pro Ala Arg Ala Pro Arg Glu Gln Asn Ser Leu GlyGlu Val 35 40 45 Asp Arg Arg Gly Pro Arg Glu Gln Thr Arg Ala Pro Ala ThrAla Ala 50 55 60 Pro Pro Arg Pro Leu Gly Ser Arg Gly Ala Glu Ala Ala GluPro Gln 65 70 75 80 Glu Gly Leu Ser Ala Thr Val Ser Ala Cys Phe Gln GluGln Gln Glu 85 90 95 Met Asn Thr Leu Gln Gly Pro Val Ser Phe Lys Asp ValAla Val Asp 100 105 110 Phe Thr Gln Glu Glu Trp Arg Gln Leu Asp Pro AspGlu Lys Ile Ala 115 120 125 Tyr Gly Asp Val Met Leu Glu Asn Tyr Ser HisLeu Val Ser Val Gly 130 135 140 Tyr Asp Tyr His Gln Ala Lys His His HisGly Val Glu Val Lys Glu 145 150 155 160 Val Glu Gln Gly Glu Glu Pro TrpIle Met Glu Gly Glu Phe Pro Cys 165 170 175 Gln His Ser Pro Glu Pro AlaLys Ala Ile Lys Pro Ile Asp Arg Lys 180 185 190 Ser Val His Gln Ile CysSer Gly Pro Val Val Leu Ser Leu Ser Thr 195 200 205 Ala Val Lys Glu LeuVal Glu Asn Ser Leu Asp Ala Gly Ala Thr Asn 210 215 220 Ile Asp Leu LysLeu Lys Asp Tyr Gly Val Asp Leu Ile Glu Val Ser 225 230 235 240 Asp AsnGly Cys Gly Val Glu Glu Glu Asn Phe Glu Gly Leu Ile Ser 245 250 255 PheSer Ser Glu Thr Ser His Met 260 42 795 DNA Homo sapiens 42 atgtgtccttggcggcctag actaggccgt cgctgtatgg tgagccccag ggaggcggat 60 ctgggcccccagaaggacac ccgcctggat ttgccccgta gcccggcccg ggcccctcgg 120 gagcagaacagccttggtga ggtggacagg aggggacctc gcgagcagac gcgcgcgcca 180 gcgacagcagccccgccccg gcctctcggg agccgggggg cagaggctgc ggagccccag 240 gagggtctatcagccacagt ctctgcatgt ttccaagagc aacaggaaat gaacacattg 300 caggggccagtgtcattcaa agatgtggct gtggatttca cccaggagga gtggcggcaa 360 ctggaccctgatgagaagat agcatacggg gatgtgatgt tggagaacta cagccatcta 420 gtttctgtggggtatgatta tcaccaagcc aaacatcatc atggagtgga ggtgaaggaa 480 gtggagcagggagaggagcc gtggataatg gaaggtgaat ttccatgtca acatagtcca 540 gaacctgctaaggccatcaa acctattgat cggaagtcag tccatcagat ttgctctggg 600 ccagtggtactgagtctaag cactgcagtg aaggagttag tagaaaacag tctggatgct 660 ggtgccactaatattgatct aaagcttaag gactatggag tggatctcat tgaagtttca 720 gacaatggatgtggggtaga agaagaaaac tttgaaggct taatctcttt cagctctgaa 780 acatcacacatgtaa 795 43 264 PRT Homo sapiens 43 Met Cys Pro Trp Arg Pro Arg Leu GlyArg Arg Cys Met Val Ser Pro 1 5 10 15 Arg Glu Ala Asp Leu Gly Pro GlnLys Asp Thr Arg Leu Asp Leu Pro 20 25 30 Arg Ser Pro Ala Arg Ala Pro ArgGlu Gln Asn Ser Leu Gly Glu Val 35 40 45 Asp Arg Arg Gly Pro Arg Glu GlnThr Arg Ala Pro Ala Thr Ala Ala 50 55 60 Pro Pro Arg Pro Leu Gly Ser ArgGly Ala Glu Ala Ala Glu Pro Gln 65 70 75 80 Glu Gly Leu Ser Ala Thr ValSer Ala Cys Phe Gln Glu Gln Gln Glu 85 90 95 Met Asn Thr Leu Gln Gly ProVal Ser Phe Lys Asp Val Ala Val Asp 100 105 110 Phe Thr Gln Glu Glu TrpArg Gln Leu Asp Pro Asp Glu Lys Ile Ala 115 120 125 Tyr Gly Asp Val MetLeu Glu Asn Tyr Ser His Leu Val Ser Val Gly 130 135 140 Tyr Asp Tyr HisGln Ala Lys His His His Gly Val Glu Val Lys Glu 145 150 155 160 Val GluGln Gly Glu Glu Pro Trp Ile Met Glu Gly Glu Phe Pro Cys 165 170 175 GlnHis Ser Pro Glu Pro Ala Lys Ala Ile Lys Pro Ile Asp Arg Lys 180 185 190Ser Val His Gln Ile Cys Ser Gly Pro Val Val Leu Ser Leu Ser Thr 195 200205 Ala Val Lys Glu Leu Val Glu Asn Ser Leu Asp Ala Gly Ala Thr Asn 210215 220 Ile Asp Leu Lys Leu Lys Asp Tyr Gly Val Asp Leu Ile Glu Val Ser225 230 235 240 Asp Asn Gly Cys Gly Val Glu Glu Glu Asn Phe Glu Gly LeuIle Ser 245 250 255 Phe Ser Ser Glu Thr Ser His Met 260 44 2772 DNAArabidopsis thaliana 44 atgcaaggag attcttctcc gtctccgacg actactagctctcctttgat aagacctata 60 aacagaaacg taattcacag aatctgttcc ggtcaagtcatcttagacct ctcttcggcc 120 gtcaaggagc ttgtcgagaa tagtctcgac gccggcgccaccagtataga gattaacctc 180 cgagactacg gcgaagacta ttttcaggtc attgacaatggttgtggcat ttccccaacc 240 aatttcaagg ttcttgcact taagcatcat acttctaaattagaggattt cacagatctt 300 ttgaatttga ctacttatgg ttttagagga gaagccttgagctctctctg tgcattggga 360 aatctcactg tggaaacaag aacaaagaat gagccagttgctacgctctt gacgtttgat 420 cattctggtt tgcttactgc tgaaaagaag actgctcgccaaattggtac cactgtcact 480 gttaggaagt tgttctctaa tttacctgta cgaagcaaagagtttaagcg gaatatacgc 540 aaagaatatg ggaagcttgt atctttattg aacgcatatgcgcttattgc gaaaggagtg 600 cggtttgtct gctctaacac gactgggaaa aacccaaagtctgttgtgct gaacacacaa 660 gggaggggtt cacttaaaga taatatcata acagttttcggcattagtac ctttacaagt 720 ctacagcctg taagtatatg tgtatcagaa gattgtagagttgaagggtt tctttccaag 780 cctggacagg gtactggacg caatttagca gatcgacagtatttctttat aaatggtcgg 840 cctgtagata tgccaaaagt cagcaagttg gtgaatgagttatataaaga tacaagttct 900 cggaaatatc cagttaccat tctggatttt attgtgcctggtggagcatg tgatttgaat 960 gtcacgcccg ataaaagaaa ggtgttcttt tctgacgagacttctgttat cggttctttg 1020 agggaaggtc tgaacgagat atattcctcc agtaatgcgtcttatattgt taataggttc 1080 gaggagaatt cggagcaacc agataaggct ggagtttcgtcgtttcagaa gaaatcaaat 1140 cttttgtcag aagggatagt tctggatgtc agttctaaaacaagactagg ggaagctatt 1200 gagaaagaaa atccatcctt aagggaggtt gaaattgataatagttcgcc aatggagaag 1260 tttaagtttg agatcaaggc atgtgggacg aagaaaggggaaggttcttt atcagtccat 1320 gatgtaactc accttgacaa gacacctagc aaaggtttgcctcagttaaa tgtgactgag 1380 aaagttactg atgcaagtaa agacttgagc agccgctctagctttgccca gtcaactttg 1440 aatacttttg ttaccatggg aaaaagaaaa catgaaaacataagcaccat cctctctgaa 1500 acacctgtcc tcagaaacca aacttctagt tatcgtgtggagaaaagcaa atttgaagtt 1560 cgtgccttag cttcaaggtg tctcgtggaa ggcgatcaacttgatgatat ggtcatctca 1620 aaggaagata tgacaccaag cgaaagagat tctgaactaggcaatcggat ttctcctgga 1680 acacaagctg ataatgttga aagacatgag agagaacatgaaaagcctat aaggtttgaa 1740 gaaccaacat cagataacac actcaccaag ggggatgtggaaagggtttc agaggacaat 1800 ccacggtgca gtcagccact gcgatctgtg gccacagtgctggattcccc agctcagtca 1860 accggtccta aaatgttttc cacattagaa tttagtttccaaaacctcag gacaaggagg 1920 ttagagaggc tgtcgagatt gcagtccaca ggttatgtatctaaatgtat gaatacgcca 1980 cagcctaaaa agtgctttgc cgctgcaaca ttagagttatctcaaccgga tgatgaagag 2040 cgaaaagcaa gggctttagc tgcagctact tctgagctggaaaggctttt tcgaaaagag 2100 gatttcagga gaatgcaggt actcgggcaa ttcaatcttgggttcatcat tgcaaaattg 2160 gagcgagatc tgttcattgt ggatcagcat gcagctgatgagaaattcaa cttcgaacat 2220 ttagcaaggt caactgtcct gaaccagcaa cccttactccagcctttgaa cttggaactc 2280 tctccagaag aagaagtaac tgtgttaatg cacatggatattatcaggga aaatggcttt 2340 cttctagagg agaatccaag tgctcctccc ggaaaacactttagactacg agccattcct 2400 tatagcaaga atatcacctt tggagtcgaa gatcttaaagacctgatctc aactctagga 2460 gataaccatg gggaatgttc ggttgctagt agctacaaaaccagcaaaac agattcgatt 2520 tgtccatcac gagtccgtgc aatgctagca tcccgagcatgcagatcatc tgtgatgatc 2580 ggagatccac tcagaaaaaa cgaaatgcag aagatagtagaacacttggc agatctcgaa 2640 tctccttgga attgcccaca cggacgacca acaatgcgtcatcttgtgga cttgacaact 2700 ttactcacat tacctgatga cgacaatgtc aatgatgatgatgatgatga tgcaaccatc 2760 tcattggcat ga 2772 45 923 PRT Arabidopsisthaliana 45 Met Gln Gly Asp Ser Ser Pro Ser Pro Thr Thr Thr Ser Ser ProLeu 1 5 10 15 Ile Arg Pro Ile Asn Arg Asn Val Ile His Arg Ile Cys SerGly Gln 20 25 30 Val Ile Leu Asp Leu Ser Ser Ala Val Lys Glu Leu Val GluAsn Ser 35 40 45 Leu Asp Ala Gly Ala Thr Ser Ile Glu Ile Asn Leu Arg AspTyr Gly 50 55 60 Glu Asp Tyr Phe Gln Val Ile Asp Asn Gly Cys Gly Ile SerPro Thr 65 70 75 80 Asn Phe Lys Val Leu Ala Leu Lys His His Thr Ser LysLeu Glu Asp 85 90 95 Phe Thr Asp Leu Leu Asn Leu Thr Thr Tyr Gly Phe ArgGly Glu Ala 100 105 110 Leu Ser Ser Leu Cys Ala Leu Gly Asn Leu Thr ValGlu Thr Arg Thr 115 120 125 Lys Asn Glu Pro Val Ala Thr Leu Leu Thr PheAsp His Ser Gly Leu 130 135 140 Leu Thr Ala Glu Lys Lys Thr Ala Arg GlnIle Gly Thr Thr Val Thr 145 150 155 160 Val Arg Lys Leu Phe Ser Asn LeuPro Val Arg Ser Lys Glu Phe Lys 165 170 175 Arg Asn Ile Arg Lys Glu TyrGly Lys Leu Val Ser Leu Leu Asn Ala 180 185 190 Tyr Ala Leu Ile Ala LysGly Val Arg Phe Val Cys Ser Asn Thr Thr 195 200 205 Gly Lys Asn Pro LysSer Val Val Leu Asn Thr Gln Gly Arg Gly Ser 210 215 220 Leu Lys Asp AsnIle Ile Thr Val Phe Gly Ile Ser Thr Phe Thr Ser 225 230 235 240 Leu GlnPro Val Ser Ile Cys Val Ser Glu Asp Cys Arg Val Glu Gly 245 250 255 PheLeu Ser Lys Pro Gly Gln Gly Thr Gly Arg Asn Leu Ala Asp Arg 260 265 270Gln Tyr Phe Phe Ile Asn Gly Arg Pro Val Asp Met Pro Lys Val Ser 275 280285 Lys Leu Val Asn Glu Leu Tyr Lys Asp Thr Ser Ser Arg Lys Tyr Pro 290295 300 Val Thr Ile Leu Asp Phe Ile Val Pro Gly Gly Ala Cys Asp Leu Asn305 310 315 320 Val Thr Pro Asp Lys Arg Lys Val Phe Phe Ser Asp Glu ThrSer Val 325 330 335 Ile Gly Ser Leu Arg Glu Gly Leu Asn Glu Ile Tyr SerSer Ser Asn 340 345 350 Ala Ser Tyr Ile Val Asn Arg Phe Glu Glu Asn SerGlu Gln Pro Asp 355 360 365 Lys Ala Gly Val Ser Ser Phe Gln Lys Lys SerAsn Leu Leu Ser Glu 370 375 380 Gly Ile Val Leu Asp Val Ser Ser Lys ThrArg Leu Gly Glu Ala Ile 385 390 395 400 Glu Lys Glu Asn Pro Ser Leu ArgGlu Val Glu Ile Asp Asn Ser Ser 405 410 415 Pro Met Glu Lys Phe Lys PheGlu Ile Lys Ala Cys Gly Thr Lys Lys 420 425 430 Gly Glu Gly Ser Leu SerVal His Asp Val Thr His Leu Asp Lys Thr 435 440 445 Pro Ser Lys Gly LeuPro Gln Leu Asn Val Thr Glu Lys Val Thr Asp 450 455 460 Ala Ser Lys AspLeu Ser Ser Arg Ser Ser Phe Ala Gln Ser Thr Leu 465 470 475 480 Asn ThrPhe Val Thr Met Gly Lys Arg Lys His Glu Asn Ile Ser Thr 485 490 495 IleLeu Ser Glu Thr Pro Val Leu Arg Asn Gln Thr Ser Ser Tyr Arg 500 505 510Val Glu Lys Ser Lys Phe Glu Val Arg Ala Leu Ala Ser Arg Cys Leu 515 520525 Val Glu Gly Asp Gln Leu Asp Asp Met Val Ile Ser Lys Glu Asp Met 530535 540 Thr Pro Ser Glu Arg Asp Ser Glu Leu Gly Asn Arg Ile Ser Pro Gly545 550 555 560 Thr Gln Ala Asp Asn Val Glu Arg His Glu Arg Glu His GluLys Pro 565 570 575 Ile Arg Phe Glu Glu Pro Thr Ser Asp Asn Thr Leu ThrLys Gly Asp 580 585 590 Val Glu Arg Val Ser Glu Asp Asn Pro Arg Cys SerGln Pro Leu Arg 595 600 605 Ser Val Ala Thr Val Leu Asp Ser Pro Ala GlnSer Thr Gly Pro Lys 610 615 620 Met Phe Ser Thr Leu Glu Phe Ser Phe GlnAsn Leu Arg Thr Arg Arg 625 630 635 640 Leu Glu Arg Leu Ser Arg Leu GlnSer Thr Gly Tyr Val Ser Lys Cys 645 650 655 Met Asn Thr Pro Gln Pro LysLys Cys Phe Ala Ala Ala Thr Leu Glu 660 665 670 Leu Ser Gln Pro Asp AspGlu Glu Arg Lys Ala Arg Ala Leu Ala Ala 675 680 685 Ala Thr Ser Glu LeuGlu Arg Leu Phe Arg Lys Glu Asp Phe Arg Arg 690 695 700 Met Gln Val LeuGly Gln Phe Asn Leu Gly Phe Ile Ile Ala Lys Leu 705 710 715 720 Glu ArgAsp Leu Phe Ile Val Asp Gln His Ala Ala Asp Glu Lys Phe 725 730 735 AsnPhe Glu His Leu Ala Arg Ser Thr Val Leu Asn Gln Gln Pro Leu 740 745 750Leu Gln Pro Leu Asn Leu Glu Leu Ser Pro Glu Glu Glu Val Thr Val 755 760765 Leu Met His Met Asp Ile Ile Arg Glu Asn Gly Phe Leu Leu Glu Glu 770775 780 Asn Pro Ser Ala Pro Pro Gly Lys His Phe Arg Leu Arg Ala Ile Pro785 790 795 800 Tyr Ser Lys Asn Ile Thr Phe Gly Val Glu Asp Leu Lys AspLeu Ile 805 810 815 Ser Thr Leu Gly Asp Asn His Gly Glu Cys Ser Val AlaSer Ser Tyr 820 825 830 Lys Thr Ser Lys Thr Asp Ser Ile Cys Pro Ser ArgVal Arg Ala Met 835 840 845 Leu Ala Ser Arg Ala Cys Arg Ser Ser Val MetIle Gly Asp Pro Leu 850 855 860 Arg Lys Asn Glu Met Gln Lys Ile Val GluHis Leu Ala Asp Leu Glu 865 870 875 880 Ser Pro Trp Asn Cys Pro His GlyArg Pro Thr Met Arg His Leu Val 885 890 895 Asp Leu Thr Thr Leu Leu ThrLeu Pro Asp Asp Asp Asn Val Asn Asp 900 905 910 Asp Asp Asp Asp Asp AlaThr Ile Ser Leu Ala 915 920 46 3466 DNA Arabidopsis thaliana 46ttcgaattct ctcagctcaa aacatcgttt ctctctcact ctctctcaca attccaaaaa 60atgcagcgcc agagatcgat tttgtctttc ttccaaaaac ccacggcggc gactacgaag 120ggtttggttt ccggcgatgc tgctagcggc gggggcggca gcggaggacc acgatttaat 180gtgaaggaag gggatgctaa aggcgacgct tctgtacgtt ttgctgtttc gaaatctgtc 240gatgaggtta gaggaacgga tactccaccg gagaaggttc cgcgtcgtgt cctgccgtct 300ggatttaagc cggctgaatc cgccggtgat gcttcgtccc tgttctccaa tattatgcat 360aagtttgtaa aagtcgatga tcgagattgt tctggagaga ggagccgaga agatgttgtt 420ccgctgaatg attcatctct atgtatgaag gctaatgatg ttattcctca atttcgttcc 480aataatggta aaactcaaga aagaaaccat gcttttagtt tcagtgggag agctgaactt 540agatcagtag aagatatagg agtagatggc gatgttcctg gtccagaaac accagggatg 600cgtccacgtg cttctcgctt gaagcgagtt ctggaggatg aaatgacttt taaggaggat 660aaggttcctg tattggactc taacaaaagg ctgaaaatgc tccaggatcc ggtttgtgga 720gagaagaaag aagtaaacga aggaaccaaa tttgaatggc ttgagtcttc tcgaatcagg 780gatgccaata gaagacgtcc tgatgatccc ctttacgata gaaagacctt acacatacca 840cctgatgttt tcaagaaaat gtctgcatca caaaagcaat attggagtgt taagagtgaa 900tatatggaca ttgtgctttt ctttaaagtg gggaaatttt atgagctgta tgagctagat 960gcggaattag gtcacaagga gcttgactgg aagatgacca tgagtggtgt gggaaaatgc 1020agacaggttg gtatctctga aagtgggata gatgaggcag tgcaaaagct attagctcgt 1080ggatataaag ttggacgaat cgagcagcta gaaacatctg accaagcaaa agccagaggt 1140gctaatacta taattccaag gaagctagtt caggtattaa ctccatcaac agcaagcgag 1200ggaaacatcg ggcctgatgc cgtccatctt cttgctataa aagagatcaa aatggagcta 1260caaaagtgtt caactgtgta tggatttgct tttgttgact gtgctgcctt gaggttttgg 1320gttgggtcca tcagcgatga tgcatcatgt gctgctcttg gagcgttatt gatgcaggtt 1380tctccaaagg aagtgttata tgacagtaaa gggctatcaa gagaagcaca aaaggctcta 1440aggaaatata cgttgacagg gtctacggcg gtacagttgg ctccagtacc acaagtaatg 1500ggggatacag atgctgctgg agttagaaat ataatagaat ctaacggata ctttaaaggt 1560tcttctgaat catggaactg tgctgttgat ggtctaaatg aatgtgatgt tgcccttagt 1620gctcttggag agctaattaa tcatctgtct aggctaaagc tagaagatgt acttaagcat 1680ggggatattt ttccatacca agtttacagg ggttgtctca gaattgatgg ccagacgatg 1740gtaaatcttg agatatttaa caatagctgt gatggtgtcc ttcagggacc cttgaacaaa 1800tatcttgaaa actgtgttag tccaactggt aagcgactct taaggaattg gatctgccat 1860ccactcaaag atgtagaaag catcaataaa cggcttgatg tagttgaaga attcacggca 1920aactcagaaa gtatgcaaat cactggccag tatctccaca aacttccaga cttagaaaga 1980ctgctcggac gcatcaagtc tagcgttcga tcatcagcct ctgtgttgcc tgctcttctg 2040gggaaaaaag tgctgaaaca acgagttaaa gcatttgggc aaattgtgaa agggttcaga 2100agtggaattg atctgttgtt ggctctacag aaggaatcaa atatgatgag tttgctttat 2160aaactctgta aacttcctat attagtagga aaaagcgggc tagagttatt tctttctcaa 2220ttcgaagcag ccatagatag cgactttcca aattatcaga accaagatgt gacagatgaa 2280aacgctgaaa ctctcacaat acttatcgaa ctttttatcg aaagagcaac tcaatggtct 2340gaggtcattc acaccataag ctgcctagat gtcctgagat cttttgcaat cgcagcaagt 2400ctctctgctg gaagcatggc caggcctgtt atttttcccg aatcagaagc tacagatcag 2460aatcagaaaa caaaagggcc aatacttaaa atccaaggac tatggcatcc atttgcagtt 2520gcagccgatg gtcaattgcc tgttccgaat gatatactcc ttggcgaggc tagaagaagc 2580agtggcagca ttcatcctcg gtcattgtta ctgacgggac caaacatggg cggaaaatca 2640actcttcttc gtgcaacatg tctggccgtt atctttgccc aacttggctg ctacgtgccg 2700tgtgagtctt gcgaaatctc cctcgtggat actatcttca caaggcttgg cgcatctgat 2760agaatcatga caggagagag tacctttttg gtagaatgca ctgagacagc gtcagttctt 2820cagaatgcaa ctcaggattc actagtaatc cttgacgaac tgggcagagg aactagtact 2880ttcgatggat acgccattgc atactcggtt tttcgtcacc tggtagagaa agttcaatgt 2940cggatgctct ttgcaacaca ttaccaccct ctcaccaagg aattcgcgtc tcacccacgt 3000gtcacctcga aacacatggc ttgcgcattc aaatcaagat ctgattatca accacgtggt 3060tgtgatcaag acctagtgtt cttgtaccgt ttaaccgagg gagcttgtcc tgagagctac 3120ggacttcaag tggcactcat ggctggaata ccaaaccaag tggttgaaac agcatcaggt 3180gctgctcaag ccatgaagag atcaattggg gaaaacttca agtcaagtga gctaagatct 3240gagttctcaa gtctgcatga agactggctc aagtcattgg tgggtatttc tcgagtcgcc 3300cacaacaatg cccccattgg cgaagatgac tacgacactt tgttttgctt atggcatgag 3360atcaaatcct cttactgtgt tcccaaataa atggctatga cataacacta tctgaagctc 3420gttaagtctt ttgcttctct gatgtttatt cctcttaaaa aatgcg 3466 47 1109 PRTArabidopsis thaliana 47 Met Gln Arg Gln Arg Ser Ile Leu Ser Phe Phe GlnLys Pro Thr Ala 1 5 10 15 Ala Thr Thr Lys Gly Leu Val Ser Gly Asp AlaAla Ser Gly Gly Gly 20 25 30 Gly Ser Gly Gly Pro Arg Phe Asn Val Lys GluGly Asp Ala Lys Gly 35 40 45 Asp Ala Ser Val Arg Phe Ala Val Ser Lys SerVal Asp Glu Val Arg 50 55 60 Gly Thr Asp Thr Pro Pro Glu Lys Val Pro ArgArg Val Leu Pro Ser 65 70 75 80 Gly Phe Lys Pro Ala Glu Ser Ala Gly AspAla Ser Ser Leu Phe Ser 85 90 95 Asn Ile Met His Lys Phe Val Lys Val AspAsp Arg Asp Cys Ser Gly 100 105 110 Glu Arg Ser Arg Glu Asp Val Val ProLeu Asn Asp Ser Ser Leu Cys 115 120 125 Met Lys Ala Asn Asp Val Ile ProGln Phe Arg Ser Asn Asn Gly Lys 130 135 140 Thr Gln Glu Arg Asn His AlaPhe Ser Phe Ser Gly Arg Ala Glu Leu 145 150 155 160 Arg Ser Val Glu AspIle Gly Val Asp Gly Asp Val Pro Gly Pro Glu 165 170 175 Thr Pro Gly MetArg Pro Arg Ala Ser Arg Leu Lys Arg Val Leu Glu 180 185 190 Asp Glu MetThr Phe Lys Glu Asp Lys Val Pro Val Leu Asp Ser Asn 195 200 205 Lys ArgLeu Lys Met Leu Gln Asp Pro Val Cys Gly Glu Lys Lys Glu 210 215 220 ValAsn Glu Gly Thr Lys Phe Glu Trp Leu Glu Ser Ser Arg Ile Arg 225 230 235240 Asp Ala Asn Arg Arg Arg Pro Asp Asp Pro Leu Tyr Asp Arg Lys Thr 245250 255 Leu His Ile Pro Pro Asp Val Phe Lys Lys Met Ser Ala Ser Gln Lys260 265 270 Gln Tyr Trp Ser Val Lys Ser Glu Tyr Met Asp Ile Val Leu PhePhe 275 280 285 Lys Val Gly Lys Phe Tyr Glu Leu Tyr Glu Leu Asp Ala GluLeu Gly 290 295 300 His Lys Glu Leu Asp Trp Lys Met Thr Met Ser Gly ValGly Lys Cys 305 310 315 320 Arg Gln Val Gly Ile Ser Glu Ser Gly Ile AspGlu Ala Val Gln Lys 325 330 335 Leu Leu Ala Arg Gly Tyr Lys Val Gly ArgIle Glu Gln Leu Glu Thr 340 345 350 Ser Asp Gln Ala Lys Ala Arg Gly AlaAsn Thr Ile Ile Pro Arg Lys 355 360 365 Leu Val Gln Val Leu Thr Pro SerThr Ala Ser Glu Gly Asn Ile Gly 370 375 380 Pro Asp Ala Val His Leu LeuAla Ile Lys Glu Ile Lys Met Glu Leu 385 390 395 400 Gln Lys Cys Ser ThrVal Tyr Gly Phe Ala Phe Val Asp Cys Ala Ala 405 410 415 Leu Arg Phe TrpVal Gly Ser Ile Ser Asp Asp Ala Ser Cys Ala Ala 420 425 430 Leu Gly AlaLeu Leu Met Gln Val Ser Pro Lys Glu Val Leu Tyr Asp 435 440 445 Ser LysGly Leu Ser Arg Glu Ala Gln Lys Ala Leu Arg Lys Tyr Thr 450 455 460 LeuThr Gly Ser Thr Ala Val Gln Leu Ala Pro Val Pro Gln Val Met 465 470 475480 Gly Asp Thr Asp Ala Ala Gly Val Arg Asn Ile Ile Glu Ser Asn Gly 485490 495 Tyr Phe Lys Gly Ser Ser Glu Ser Trp Asn Cys Ala Val Asp Gly Leu500 505 510 Asn Glu Cys Asp Val Ala Leu Ser Ala Leu Gly Glu Leu Ile AsnHis 515 520 525 Leu Ser Arg Leu Lys Leu Glu Asp Val Leu Lys His Gly AspIle Phe 530 535 540 Pro Tyr Gln Val Tyr Arg Gly Cys Leu Arg Ile Asp GlyGln Thr Met 545 550 555 560 Val Asn Leu Glu Ile Phe Asn Asn Ser Cys AspGly Val Leu Gln Gly 565 570 575 Pro Leu Asn Lys Tyr Leu Glu Asn Cys ValSer Pro Thr Gly Lys Arg 580 585 590 Leu Leu Arg Asn Trp Ile Cys His ProLeu Lys Asp Val Glu Ser Ile 595 600 605 Asn Lys Arg Leu Asp Val Val GluGlu Phe Thr Ala Asn Ser Glu Ser 610 615 620 Met Gln Ile Thr Gly Gln TyrLeu His Lys Leu Pro Asp Leu Glu Arg 625 630 635 640 Leu Leu Gly Arg IleLys Ser Ser Val Arg Ser Ser Ala Ser Val Leu 645 650 655 Pro Ala Leu LeuGly Lys Lys Val Leu Lys Gln Arg Val Lys Ala Phe 660 665 670 Gly Gln IleVal Lys Gly Phe Arg Ser Gly Ile Asp Leu Leu Leu Ala 675 680 685 Leu GlnLys Glu Ser Asn Met Met Ser Leu Leu Tyr Lys Leu Cys Lys 690 695 700 LeuPro Ile Leu Val Gly Lys Ser Gly Leu Glu Leu Phe Leu Ser Gln 705 710 715720 Phe Glu Ala Ala Ile Asp Ser Asp Phe Pro Asn Tyr Gln Asn Gln Asp 725730 735 Val Thr Asp Glu Asn Ala Glu Thr Leu Thr Ile Leu Ile Glu Leu Phe740 745 750 Ile Glu Arg Ala Thr Gln Trp Ser Glu Val Ile His Thr Ile SerCys 755 760 765 Leu Asp Val Leu Arg Ser Phe Ala Ile Ala Ala Ser Leu SerAla Gly 770 775 780 Ser Met Ala Arg Pro Val Ile Phe Pro Glu Ser Glu AlaThr Asp Gln 785 790 795 800 Asn Gln Lys Thr Lys Gly Pro Ile Leu Lys IleGln Gly Leu Trp His 805 810 815 Pro Phe Ala Val Ala Ala Asp Gly Gln LeuPro Val Pro Asn Asp Ile 820 825 830 Leu Leu Gly Glu Ala Arg Arg Ser SerGly Ser Ile His Pro Arg Ser 835 840 845 Leu Leu Leu Thr Gly Pro Asn MetGly Gly Lys Ser Thr Leu Leu Arg 850 855 860 Ala Thr Cys Leu Ala Val IlePhe Ala Gln Leu Gly Cys Tyr Val Pro 865 870 875 880 Cys Glu Ser Cys GluIle Ser Leu Val Asp Thr Ile Phe Thr Arg Leu 885 890 895 Gly Ala Ser AspArg Ile Met Thr Gly Glu Ser Thr Phe Leu Val Glu 900 905 910 Cys Thr GluThr Ala Ser Val Leu Gln Asn Ala Thr Gln Asp Ser Leu 915 920 925 Val IleLeu Asp Glu Leu Gly Arg Gly Thr Ser Thr Phe Asp Gly Tyr 930 935 940 AlaIle Ala Tyr Ser Val Phe Arg His Leu Val Glu Lys Val Gln Cys 945 950 955960 Arg Met Leu Phe Ala Thr His Tyr His Pro Leu Thr Lys Glu Phe Ala 965970 975 Ser His Pro Arg Val Thr Ser Lys His Met Ala Cys Ala Phe Lys Ser980 985 990 Arg Ser Asp Tyr Gln Pro Arg Gly Cys Asp Gln Asp Leu Val PheLeu 995 1000 1005 Tyr Arg Leu Thr Glu Gly Ala Cys Pro Glu Ser Tyr GlyLeu Gln 1010 1015 1020 Val Ala Leu Met Ala Gly Ile Pro Asn Gln Val ValGlu Thr Ala 1025 1030 1035 Ser Gly Ala Ala Gln Ala Met Lys Arg Ser IleGly Glu Asn Phe 1040 1045 1050 Lys Ser Ser Glu Leu Arg Ser Glu Phe SerSer Leu His Glu Asp 1055 1060 1065 Trp Leu Lys Ser Leu Val Gly Ile SerArg Val Ala His Asn Asn 1070 1075 1080 Ala Pro Ile Gly Glu Asp Asp TyrAsp Thr Leu Phe Cys Leu Trp 1085 1090 1095 His Glu Ile Lys Ser Ser TyrCys Val Pro Lys 1100 1105 48 5307 DNA Arabidopsis thaliana 48 aaagataagttcatacgact tttgtggctc atcaaaggcc atcatcgtcc tctatataca 60 atttagtgctttatagtaca aaaccttcca cttccctttg tccaaagttt tccaatttaa 120 tttataaacaggaataatat tatctatata ataaagtgaa aaataactat cattgtccaa 180 ataatttggtcgttgatcat gttactacaa agaaatgaaa tccttagtag aagtatatat 240 atatatatatttgtaacaca ctcaaaatgg taggtgttgt tacagacaga tgttcgttag 300 cccagtaagcccaatatgag atttaatggg ccttgatatt ttatagacca aacattgaaa 360 cattgcacgcctggtctcaa agaacgttaa tacacgcgcc gccggttgcc gccaatccgc 420 tttcccgccaaattcgacac cataaatttc ttctagtcgc tttcgattcc agttccactg 480 aaaaaccacgaaagaagaac atttgcaccg tagttgcaga aggtaggtga aggatttagc 540 tttctctatcttccaatgga gggtaatttc gaggaacaga acaagcttcc ggagctgaaa 600 ttgggtaatgttaaacccta gttttttttt tctttctcat tttcgtattc gatttcccaa 660 ttgggtttatgggttttgta aaaggtctga tatttgttat gcattttttt tttaattttt 720 ggaagatgcaaagcaagctc aagggtttct ctcgttctac aaaaccctac caaatgtaag 780 ttctcgttttctttcgattt ctgggagaag ttagagcttg tacagtgcct ctaattgcaa 840 taaataacaccaattctagt cggaaagtag atgctttaaa attagggttt gaagcaattg 900 tagacattttgttcattggg aagcgaatta ggaaaaaagg cttaagattt tttagcaatt 960 tctcgatctttgcttatgtg ggttttgatt gttctttgct tcaggatacg agagctgtta 1020 gattctttgatcgcaaggtg agttcattgt tctcaaatgg tctagacttt ggttgtttaa 1080 atgtcgtcattgatttatgg aaattttttg aatgcatttg caggattatt atacagctca 1140 tggtgaaaattcagttttca ttgcaaagac ttattatcat acaaccactg ctctacgtca 1200 gctcgggagtggttcaaatg ctctttcaag cgtaagcatt agtaggaaca tgttcgaaac 1260 gattgctagggatcttctcc tggagcgtaa tgatcatact gtagaacttt atgaaggaag 1320 cggatcgaattggagacttg tgaaaacagg ttctcctgga aacattggaa gctttgaaga 1380 tgttttgtttgcaaacaatg aaatgcagga cacaccagtt gttgtctcca tatttccaag 1440 ttttcacgatggcagatgcg ttattgggat ggcctatgtt gatctgacta ggcgagttct 1500 tggactagctgagtttcttg atgatagccg cttcaccaat ctggagtctt cgttgattgc 1560 tctaggcgcaaaagaatgca tttttccagc tgaatccggc aaatccaatg aatgcaaaag 1620 cctgtatgattccctggaga ggtgtgccgt gatgataaca gagaggaaga aacacgagtt 1680 caaaggaagagatttagatt cagatcttaa gagattggtg aaggggaata ttgagcctgt 1740 tagagatttggtatccgggt ttgaccttgc gactcctgct ctaggtgcat tactctcgtt 1800 ttctgaacttctctcaaatg aggataacta tgggaacttc acaatccgca gatatgatat 1860 tggcggattcatgagacttg actctgcagc tatgagggcg ttgaatgtga tggagagcaa 1920 aactgatgctaataagaatt tcagtttgtt tggtctcatg aacagaacat gtaccgcagg 1980 gatgggtaagagactgcttc atatgtggct gaagcaaccc ctcgtggatt tgaatgagat 2040 taagacgagattagatatag ttcagtgctt tgttgaagaa gctgggttaa ggcaggatct 2100 tagacagcatctgaagcgaa tctcagatgt tgagaggctt ttgcgcagtc tcgagagaag 2160 aagaggtgggttacagcaca ttattaaact ctatcaggta ctttccgcac ttcaatctgc 2220 ttctctcaatgttaacaaaa ttgcattttc attgtcctaa atgtgtttat gcaactctga 2280 agttataggtatgttattaa gttcattact aattaagtct tcatcttttc tctgcagtca 2340 gctataaggcttcccttcat caaaacagct atgcaacagt acaccggaga attcgcatca 2400 ctcatcagcgagaggtacct gaaaaagctt gaggctttat cagatcaaga tcaccttgga 2460 aagttcatcgatttggttga gtgctctgta gatcttgacc agctagaaaa tggagaatac 2520 atgatatcttcaaactacga caccaaattg gcatctctga aagatcagaa agaattgctg 2580 gagcagcagattcacgaatt gcacaaaaag acagcgatag aacttgatct tcaggtcgac 2640 aaggctcttaaacttgacaa agcagcgcaa tttgggcatg tcttcaggat cacgaagaag 2700 gaagagccaaagatcaggaa gaagctgacg acacagttta tagtgctgga gactcgcaaa 2760 gacggagtgaagttcacaaa cacaaagcta aaaaaactgg gcgaccagta ccaaagtgtt 2820 gtggatgattataggagctg tcaaaaggag ctcgttgatc gtgtagttga gactgttacc 2880 agcttctctgaggtatgttt agttattcat attaagcatt ggactgttac agaattggtt 2940 gtttaaaatcatagtaaact atatgtggaa tttatatgta tattgtatgg ttataggtat 3000 ttgaggacttagctgggtta ctttctgaaa tggatgtttt gttaagcttt gctgatttgg 3060 ctgccagttgccctactcca tactgtaggc cagaaatcac ctctttggtt agtacaatct 3120 caagttgattattttgttct gaaaatgaat agttttttct ttccaagttt atgacataat 3180 gttgagagcacggttaataa attgtaggat gctggagata ttgtactaga aggaagcaga 3240 catccatgtgtagaagctca agattgggtg aatttcatac caaatgattg cagactcgta 3300 agtattgaatgtggtaaata aactgagacg tctttgtttt tcttgtttcc cttttgactt 3360 gaacaaatacttgtttgccc tttactgttc tttgaaatca gatgagaggg aagagttggt 3420 ttcaaatagtaacagggcct aacatgggag ggaagtccac tttcatccgc caggtatgat 3480 gatttcctctagttcagttt tgcttcatag acgtatgact aaagtcggtt tccggccatt 3540 ataaatcccaggttggtgtg attgtgctga tggctcaagt tggttccttt gttccttgtg 3600 ataaagcatcaatttccata agagactgca tctttgcccg tgtaggagca ggcgattgcc 3660 aagtgagtttaagtttagcc ctcaatgaac gaaaaactgc tgatatcctg aacaccctta 3720 ttccaactttttttcctttg gtgtgttagc tgcgtggagt gtcaactttt atgcaagaaa 3780 tgcttgaaaccgcatcgata ttgaaaggcg ctactgataa gtcactgata attatcgatg 3840 aacttggtcgtggaacatca acttatgatg gttttggtta gtttctctgc aatttctctt 3900 ctttcatttggatgttttta gtaagttttc tattatatat tcatttttat ggtcatatgt 3960 gagatttcagtgctcttgac atcatcgtgg tgaatatatc aggtttagct tgggctatat 4020 gtgagcatctggttcaagtg aaaagagcac caactctgtt tgctactcac ttccatgaac 4080 ttactgccttggctcaagca aactctgagg tctctggtaa cactgttggt gtggcaaact 4140 tccatgtcagcgctcacatt gacactgaaa gccgcaaact caccatgctt tacaaggtct 4200 ggtttataaattaaaaaatt gctgatctgt tgcagttaaa agtgtctctg tttttatgtt 4260 taatctaaattacttatttg attttcttac aaagatgaaa ttgaaattaa ttttgtgtgg 4320 tgtgttgtttgtctggttag gttgaaccag gggcctgtga ccagagcttt gggattcatg 4380 tggcggaatttgccaacttc cctgaaagcg tcgtggccct cgcaagagag aaagctgcag 4440 agctggaagatttctctccc tcctcgatga taatcaacaa tgaggtcttg attcatttcc 4500 ccctttgtttttggttgatg atggaatcat tctatcattc acccattctg cagtttatgc 4560 tatattattataaatctatg tgacaaagat ttaattctcg tattgttgtt tgcaggagag 4620 tgggaagagaaagagcagag aagatgatcc agatgaagta tcaagagggg cagagcgagc 4680 tcacaagtttctgaaagagt ttgcagcgat gccacttgat aaaatggagc ttaaagattc 4740 acttcaacgggtacgtgaga tgaaagatga gctagagaaa gatgctgcag actgccactg 4800 gctcaggcagtttctgtgaa gaacccctga cgttttttgg tttttggttt tgtaaatagc 4860 ttaaatcggttcttgtagtt gtggtcgttg cttgggatga aactaaatga gggcaaaaac 4920 ataattctacattttttgtt agtaaagctc gttaatttac tccctagtgc tatcaattat 4980 tttgcctattataattgttg atcaagtact tagagcaacc ccaatggttt ctaaacataa 5040 gtttcttattttatagagag aaattttatt ataaaaaaat gtgtgggttt cttgattagt 5100 gaagaaaccatctccaaaat accttatatt cttatataag gtattttgga gagaatttct 5160 aactattcaagaaacttaca taattaaata ctattatttt tattgtttta atgttaagaa 5220 acttatatttaaaaaccacc aatggaattg ctcttagcta ccatacaaat aattataaaa 5280 atatatcgaaaagtagaaga gccattt 5307 49 937 PRT Arabidopsis thaliana 49 Met Glu GlyAsn Phe Glu Glu Gln Asn Lys Leu Pro Glu Leu Lys Leu 1 5 10 15 Asp AlaLys Gln Ala Gln Gly Phe Leu Ser Phe Tyr Lys Thr Leu Pro 20 25 30 Asn AspThr Arg Ala Val Arg Phe Phe Asp Arg Lys Asp Tyr Tyr Thr 35 40 45 Ala HisGly Glu Asn Ser Val Phe Ile Ala Lys Thr Tyr Tyr His Thr 50 55 60 Thr ThrAla Leu Arg Gln Leu Gly Ser Gly Ser Asn Ala Leu Ser Ser 65 70 75 80 ValSer Ile Ser Arg Asn Met Phe Glu Thr Ile Ala Arg Asp Leu Leu 85 90 95 LeuGlu Arg Asn Asp His Thr Val Glu Leu Tyr Glu Gly Ser Gly Ser 100 105 110Asn Trp Arg Leu Val Lys Thr Gly Ser Pro Gly Asn Ile Gly Ser Phe 115 120125 Glu Asp Val Leu Phe Ala Asn Asn Glu Met Gln Asp Thr Pro Val Val 130135 140 Val Ser Ile Phe Pro Ser Phe His Asp Gly Arg Cys Val Ile Gly Met145 150 155 160 Ala Tyr Val Asp Leu Thr Arg Arg Val Leu Gly Leu Ala GluPhe Leu 165 170 175 Asp Asp Ser Arg Phe Thr Asn Leu Glu Ser Ser Leu IleAla Leu Gly 180 185 190 Ala Lys Glu Cys Ile Phe Pro Ala Glu Ser Gly LysSer Asn Glu Cys 195 200 205 Lys Ser Leu Tyr Asp Ser Leu Glu Arg Cys AlaVal Met Ile Thr Glu 210 215 220 Arg Lys Lys His Glu Phe Lys Gly Arg AspLeu Asp Ser Asp Leu Lys 225 230 235 240 Arg Leu Val Lys Gly Asn Ile GluPro Val Arg Asp Leu Val Ser Gly 245 250 255 Phe Asp Leu Ala Thr Pro AlaLeu Gly Ala Leu Leu Ser Phe Ser Glu 260 265 270 Leu Leu Ser Asn Glu AspAsn Tyr Gly Asn Phe Thr Ile Arg Arg Tyr 275 280 285 Asp Ile Gly Gly PheMet Arg Leu Asp Ser Ala Ala Met Arg Ala Leu 290 295 300 Asn Val Met GluSer Lys Thr Asp Ala Asn Lys Asn Phe Ser Leu Phe 305 310 315 320 Gly LeuMet Asn Arg Thr Cys Thr Ala Gly Met Gly Lys Arg Leu Leu 325 330 335 HisMet Trp Leu Lys Gln Pro Leu Val Asp Leu Asn Glu Ile Lys Thr 340 345 350Arg Leu Asp Ile Val Gln Cys Phe Val Glu Glu Ala Gly Leu Arg Gln 355 360365 Asp Leu Arg Gln His Leu Lys Arg Ile Ser Asp Val Glu Arg Leu Leu 370375 380 Arg Ser Leu Glu Arg Arg Arg Gly Gly Leu Gln His Ile Ile Lys Leu385 390 395 400 Tyr Gln Ser Ala Ile Arg Leu Pro Phe Ile Lys Thr Ala MetGln Gln 405 410 415 Tyr Thr Gly Glu Phe Ala Ser Leu Ile Ser Glu Arg TyrLeu Lys Lys 420 425 430 Leu Glu Ala Leu Ser Asp Gln Asp His Leu Gly LysPhe Ile Asp Leu 435 440 445 Val Glu Cys Ser Val Asp Leu Asp Gln Leu GluAsn Gly Glu Tyr Met 450 455 460 Ile Ser Ser Asn Tyr Asp Thr Lys Leu AlaSer Leu Lys Asp Gln Lys 465 470 475 480 Glu Leu Leu Glu Gln Gln Ile HisGlu Leu His Lys Lys Thr Ala Ile 485 490 495 Glu Leu Asp Leu Gln Val AspLys Ala Leu Lys Leu Asp Lys Ala Ala 500 505 510 Gln Phe Gly His Val PheArg Ile Thr Lys Lys Glu Glu Pro Lys Ile 515 520 525 Arg Lys Lys Leu ThrThr Gln Phe Ile Val Leu Glu Thr Arg Lys Asp 530 535 540 Gly Val Lys PheThr Asn Thr Lys Leu Lys Lys Leu Gly Asp Gln Tyr 545 550 555 560 Gln SerVal Val Asp Asp Tyr Arg Ser Cys Gln Lys Glu Leu Val Asp 565 570 575 ArgVal Val Glu Thr Val Thr Ser Phe Ser Glu Val Phe Glu Asp Leu 580 585 590Ala Gly Leu Leu Ser Glu Met Asp Val Leu Leu Ser Phe Ala Asp Leu 595 600605 Ala Ala Ser Cys Pro Thr Pro Tyr Cys Arg Pro Glu Ile Thr Ser Leu 610615 620 Asp Ala Gly Asp Ile Val Leu Glu Gly Ser Arg His Pro Cys Val Glu625 630 635 640 Ala Gln Asp Trp Val Asn Phe Ile Pro Asn Asp Cys Arg LeuMet Arg 645 650 655 Gly Lys Ser Trp Phe Gln Ile Val Thr Gly Pro Asn MetGly Gly Lys 660 665 670 Ser Thr Phe Ile Arg Gln Val Gly Val Ile Val LeuMet Ala Gln Val 675 680 685 Gly Ser Phe Val Pro Cys Asp Lys Ala Ser IleSer Ile Arg Asp Cys 690 695 700 Ile Phe Ala Arg Val Gly Ala Gly Asp CysGln Leu Arg Gly Val Ser 705 710 715 720 Thr Phe Met Gln Glu Met Leu GluThr Ala Ser Ile Leu Lys Gly Ala 725 730 735 Thr Asp Lys Ser Leu Ile IleIle Asp Glu Leu Gly Arg Gly Thr Ser 740 745 750 Thr Tyr Asp Gly Phe GlyLeu Ala Trp Ala Ile Cys Glu His Leu Val 755 760 765 Gln Val Lys Arg AlaPro Thr Leu Phe Ala Thr His Phe His Glu Leu 770 775 780 Thr Ala Leu AlaGln Ala Asn Ser Glu Val Ser Gly Asn Thr Val Gly 785 790 795 800 Val AlaAsn Phe His Val Ser Ala His Ile Asp Thr Glu Ser Arg Lys 805 810 815 LeuThr Met Leu Tyr Lys Val Glu Pro Gly Ala Cys Asp Gln Ser Phe 820 825 830Gly Ile His Val Ala Glu Phe Ala Asn Phe Pro Glu Ser Val Val Ala 835 840845 Leu Ala Arg Glu Lys Ala Ala Glu Leu Glu Asp Phe Ser Pro Ser Ser 850855 860 Met Ile Ile Asn Asn Glu Glu Ser Gly Lys Arg Lys Ser Arg Glu Asp865 870 875 880 Asp Pro Asp Glu Val Ser Arg Gly Ala Glu Arg Ala His LysPhe Leu 885 890 895 Lys Glu Phe Ala Ala Met Pro Leu Asp Lys Met Glu LeuLys Asp Ser 900 905 910 Leu Gln Arg Val Arg Glu Met Lys Asp Glu Leu GluLys Asp Ala Ala 915 920 925 Asp Cys His Trp Leu Arg Gln Phe Leu 930 93550 3521 DNA Arabidopsis thaliana 50 ctaagaaagc gcgcgaaaat tggcaacccaagttcgccat agccacgacc acgaccttcc 60 atttctctta aacggaggag attacgaataaagcaattat gggcaagcaa aagcagcaga 120 cgatttctcg tttcttcgct cccaaacccaaatccccgac tcacgaaccg aatccggtag 180 ccgaatcatc aacaccgcca ccgaagatatccgccactgt atccttctct ccttccaagc 240 gtaagcttct ctccgaccac ctcgccgccgcgtcacccaa aaagcctaaa ctttctcctc 300 acactcaaaa cccagtaccc gatcccaatttacaccaaag atttctccag agatttctgg 360 aaccctcgcc ggaggaatat gttcccgaaacgtcatcatc gaggaaatac acaccattgg 420 aacagcaagt ggtggagcta aagagcaagtacccagatgt ggttttgatg gtggaagttg 480 gttacaggta cagattcttc ggagaagacgcggagatcgc agcacgcgtg ttgggtattt 540 acgctcatat ggatcacaat ttcatgacggcgagtgtgcc aacatttcga ttgaatttcc 600 atgtgagaag actggtgaat gcaggatacaagattggtgt agtgaagcag actgaaactg 660 cagccattaa gtcccatggt gcaaaccggaccggcccttt tttccgggga ctgtcggcgt 720 tgtataccaa agccacgctt gaagcggctgaggatataag tggtggttgt ggtggtgaag 780 aaggttttgg ttcacagagt aatttcttggtttgtgttgt ggatgagaga gttaagtcgg 840 agacattagg ctgtggtatt gaaatgagttttgatgttag agtcggtgtt gttggcgttg 900 aaatttcgac aggtgaagtt gtttatgaagagttcaatga taatttcatg agaagtggat 960 tagaggctgt gattttgagc ttgtcaccagctgagctgtt gcttggccag cctctttcac 1020 aacaaactga gaagtttttg gtggcacatgctggacctac ctcaaacgtt cgagtggaac 1080 gtgcctcact ggattgtttc agcaatggtaatgcagtaga tgaggttatt tcattatgtg 1140 aaaaaatcag cgcaggtaac ttagaagatgataaagaaat gaagctggag gctgctgaaa 1200 aaggaatgtc ttgcttgaca gttcatacaattatgaacat gccacatctg actgttcaag 1260 ccctcgccct aacgttttgc catctcaaacagtttggatt tgaaaggatc ctttaccaag 1320 gggcctcatt tcgctctttg tcaagtaacacagagatgac tctctcagcc aatactctgc 1380 aacagttgga ggttgtgaaa aataattcagatggatcgga atctggctcc ttattccata 1440 atatgaatca cacacttaca gtatatggttccaggcttct tagacactgg gtgactcatc 1500 ctctatgcga tagaaatttg atatctgctcggcttgatgc tgtttctgag atttctgctt 1560 gcatgggatc tcatagttct tcccagctcagcagtgagtt ggttgaagaa ggttctgaga 1620 gagcaattgt atcacctgag ttttatctcgtgctctcctc agtcttgaca gctatgtcta 1680 gatcatctga tattcaacgt ggaataacaagaatctttca tcggactgct aaagccacag 1740 agttcattgc agttatggaa gctattttacttgcggggaa gcaaattcag cggcttggca 1800 taaagcaaga ctctgaaatg aggagtatgcaatctgcaac tgtgcgatct actcttttga 1860 gaaaattgat ttctgttatt tcatcccctgttgtggttga caatgccgga aaacttctct 1920 ctgccctaaa taaggaagcg gctgttcgaggtgacttgct cgacatacta atcacttcca 1980 gcgaccaatt tcctgagctt gctgaagctcgccaagcagt tttagtcatc agggaaaagc 2040 tggattcctc gatagcttca tttcgcaagaagctcgctat tcgaaatttg gaatttcttc 2100 aagtgtcggg gatcacacat ttgatagagctgcccgttga ttccaaggtc cctatgaatt 2160 gggtgaaagt aaatagcacc aagaagactattcgatatca tcccccagaa atagtagctg 2220 gcttggatga gctagctcta gcaactgaacatcttgccat tgtgaaccga gcttcgtggg 2280 atagtttcct caagagtttc agtagatactacacagattt taaggctgcc gttcaagctc 2340 ttgctgcact ggactgtttg cactccctttcaactctatc tagaaacaag aactatgtcc 2400 gtcccgagtt tgtggatgac tgtgaaccagttgagataaa catacagtct ggtcgtcatc 2460 ctgtactgga gactatatta caagataacttcgtcccaaa tgacacaatt ttgcatgcag 2520 aaggggaata ttgccaaatt atcaccggacctaacatggg aggaaagagc tgctatatcc 2580 gtcaagttgc tttaatttcc ataatggctcaggttggttc ctttgtacca gcgtcattcg 2640 ccaagctgca cgtgcttgat ggtgttttcactcggatggg tgcttcagac agtatccagc 2700 atggcagaag tacctttcta gaagaattaagtgaagcgtc acacataatc agaacctgtt 2760 cttctcgttc gcttgttata ttagatgagcttggaagagg cactagcaca cacgacggtg 2820 tagccattgc ctatgcaaca ttacagcatctcctagcaga aaagagatgt ttggttcttt 2880 ttgtcacgca ttaccctgaa atagctgagatcagtaacgg attcccaggt tctgttggga 2940 cataccatgt ctcgtatctg acattgcagaaggataaagg cagttatgat catgatgatg 3000 tgacctacct atataagctt gtgcgtggtctttgcagcag gagctttggt tttaaggttg 3060 ctcagcttgc ccagatacct ccatcatgtatacgtcgagc catttcaatg gctgcaaaat 3120 tggaagctga ggtacgtgca agagagagaaatacacgcat gggagaacca gaaggacatg 3180 aagaaccgag aggcgcagaa gaatctatttcggctctagg tgacttgttt gcagacctga 3240 aatttgctct ctctgaagag gacccttggaaagcattcga gtttttaaag catgcttgga 3300 agattgctgg caaaatcaga ctaaaaccaacttgttcatt ttgatttaat cttaacatta 3360 tagcaactgc aaggtcttga tcatctgttagttgcgtact aacttatgtg tattagtata 3420 acaagaaaag agaattagag agatggattctaatccggtg ttgcagtaca tcttttctcc 3480 acccgcataa aaaaaaaaaa aaaaaaaaaaaaaaaaaaaa a 3521 51 1081 PRT Arabidopsis thaliana 51 Met Gly Lys GlnLys Gln Gln Thr Ile Ser Arg Phe Phe Ala Pro Lys 1 5 10 15 Pro Lys SerPro Thr His Glu Pro Asn Pro Val Ala Glu Ser Ser Thr 20 25 30 Pro Pro ProLys Ile Ser Ala Thr Val Ser Phe Ser Pro Ser Lys Arg 35 40 45 Lys Leu LeuSer Asp His Leu Ala Ala Ala Ser Pro Lys Lys Pro Lys 50 55 60 Leu Ser ProHis Thr Gln Asn Pro Val Pro Asp Pro Asn Leu His Gln 65 70 75 80 Arg PheLeu Gln Arg Phe Leu Glu Pro Ser Pro Glu Glu Tyr Val Pro 85 90 95 Glu ThrSer Ser Ser Arg Lys Tyr Thr Pro Leu Glu Gln Gln Val Val 100 105 110 GluLeu Lys Ser Lys Tyr Pro Asp Val Val Leu Met Val Glu Val Gly 115 120 125Tyr Arg Tyr Arg Phe Phe Gly Glu Asp Ala Glu Ile Ala Ala Arg Val 130 135140 Leu Gly Ile Tyr Ala His Met Asp His Asn Phe Met Thr Ala Ser Val 145150 155 160 Pro Thr Phe Arg Leu Asn Phe His Val Arg Arg Leu Val Asn AlaGly 165 170 175 Tyr Lys Ile Gly Val Val Lys Gln Thr Glu Thr Ala Ala IleLys Ser 180 185 190 His Gly Ala Asn Arg Thr Gly Pro Phe Phe Arg Gly LeuSer Ala Leu 195 200 205 Tyr Thr Lys Ala Thr Leu Glu Ala Ala Glu Asp IleSer Gly Gly Cys 210 215 220 Gly Gly Glu Glu Gly Phe Gly Ser Gln Ser AsnPhe Leu Val Cys Val 225 230 235 240 Val Asp Glu Arg Val Lys Ser Glu ThrLeu Gly Cys Gly Ile Glu Met 245 250 255 Ser Phe Asp Val Arg Val Gly ValVal Gly Val Glu Ile Ser Thr Gly 260 265 270 Glu Val Val Tyr Glu Glu PheAsn Asp Asn Phe Met Arg Ser Gly Leu 275 280 285 Glu Ala Val Ile Leu SerLeu Ser Pro Ala Glu Leu Leu Leu Gly Gln 290 295 300 Pro Leu Ser Gln GlnThr Glu Lys Phe Leu Val Ala His Ala Gly Pro 305 310 315 320 Thr Ser AsnVal Arg Val Glu Arg Ala Ser Leu Asp Cys Phe Ser Asn 325 330 335 Gly AsnAla Val Asp Glu Val Ile Ser Leu Cys Glu Lys Ile Ser Ala 340 345 350 GlyAsn Leu Glu Asp Asp Lys Glu Met Lys Leu Glu Ala Ala Glu Lys 355 360 365Gly Met Ser Cys Leu Thr Val His Thr Ile Met Asn Met Pro His Leu 370 375380 Thr Val Gln Ala Leu Ala Leu Thr Phe Cys His Leu Lys Gln Phe Gly 385390 395 400 Phe Glu Arg Ile Leu Tyr Gln Gly Ala Ser Phe Arg Ser Leu SerSer 405 410 415 Asn Thr Glu Met Thr Leu Ser Ala Asn Thr Leu Gln Gln LeuGlu Val 420 425 430 Val Lys Asn Asn Ser Asp Gly Ser Glu Ser Gly Ser LeuPhe His Asn 435 440 445 Met Asn His Thr Leu Thr Val Tyr Gly Ser Arg LeuLeu Arg His Trp 450 455 460 Val Thr His Pro Leu Cys Asp Arg Asn Leu IleSer Ala Arg Leu Asp 465 470 475 480 Ala Val Ser Glu Ile Ser Ala Cys MetGly Ser His Ser Ser Ser Gln 485 490 495 Leu Ser Ser Glu Leu Val Glu GluGly Ser Glu Arg Ala Ile Val Ser 500 505 510 Pro Glu Phe Tyr Leu Val LeuSer Ser Val Leu Thr Ala Met Ser Arg 515 520 525 Ser Ser Asp Ile Gln ArgGly Ile Thr Arg Ile Phe His Arg Thr Ala 530 535 540 Lys Ala Thr Glu PheIle Ala Val Met Glu Ala Ile Leu Leu Ala Gly 545 550 555 560 Lys Gln IleGln Arg Leu Gly Ile Lys Gln Asp Ser Glu Met Arg Ser 565 570 575 Met GlnSer Ala Thr Val Arg Ser Thr Leu Leu Arg Lys Leu Ile Ser 580 585 590 ValIle Ser Ser Pro Val Val Val Asp Asn Ala Gly Lys Leu Leu Ser 595 600 605Ala Leu Asn Lys Glu Ala Ala Val Arg Gly Asp Leu Leu Asp Ile Leu 610 615620 Ile Thr Ser Ser Asp Gln Phe Pro Glu Leu Ala Glu Ala Arg Gln Ala 625630 635 640 Val Leu Val Ile Arg Glu Lys Leu Asp Ser Ser Ile Ala Ser PheArg 645 650 655 Lys Lys Leu Ala Ile Arg Asn Leu Glu Phe Leu Gln Val SerGly Ile 660 665 670 Thr His Leu Ile Glu Leu Pro Val Asp Ser Lys Val ProMet Asn Trp 675 680 685 Val Lys Val Asn Ser Thr Lys Lys Thr Ile Arg TyrHis Pro Pro Glu 690 695 700 Ile Val Ala Gly Leu Asp Glu Leu Ala Leu AlaThr Glu His Leu Ala 705 710 715 720 Ile Val Asn Arg Ala Ser Trp Asp SerPhe Leu Lys Ser Phe Ser Arg 725 730 735 Tyr Tyr Thr Asp Phe Lys Ala AlaVal Gln Ala Leu Ala Ala Leu Asp 740 745 750 Cys Leu His Ser Leu Ser ThrLeu Ser Arg Asn Lys Asn Tyr Val Arg 755 760 765 Pro Glu Phe Val Asp AspCys Glu Pro Val Glu Ile Asn Ile Gln Ser 770 775 780 Gly Arg His Pro ValLeu Glu Thr Ile Leu Gln Asp Asn Phe Val Pro 785 790 795 800 Asn Asp ThrIle Leu His Ala Glu Gly Glu Tyr Cys Gln Ile Ile Thr 805 810 815 Gly ProAsn Met Gly Gly Lys Ser Cys Tyr Ile Arg Gln Val Ala Leu 820 825 830 IleSer Ile Met Ala Gln Val Gly Ser Phe Val Pro Ala Ser Phe Ala 835 840 845Lys Leu His Val Leu Asp Gly Val Phe Thr Arg Met Gly Ala Ser Asp 850 855860 Ser Ile Gln His Gly Arg Ser Thr Phe Leu Glu Glu Leu Ser Glu Ala 865870 875 880 Ser His Ile Ile Arg Thr Cys Ser Ser Arg Ser Leu Val Ile LeuAsp 885 890 895 Glu Leu Gly Arg Gly Thr Ser Thr His Asp Gly Val Ala IleAla Tyr 900 905 910 Ala Thr Leu Gln His Leu Leu Ala Glu Lys Arg Cys LeuVal Leu Phe 915 920 925 Val Thr His Tyr Pro Glu Ile Ala Glu Ile Ser AsnGly Phe Pro Gly 930 935 940 Ser Val Gly Thr Tyr His Val Ser Tyr Leu ThrLeu Gln Lys Asp Lys 945 950 955 960 Gly Ser Tyr Asp His Asp Asp Val ThrTyr Leu Tyr Lys Leu Val Arg 965 970 975 Gly Leu Cys Ser Arg Ser Phe GlyPhe Lys Val Ala Gln Leu Ala Gln 980 985 990 Ile Pro Pro Ser Cys Ile ArgArg Ala Ile Ser Met Ala Ala Lys Leu 995 1000 1005 Glu Ala Glu Val ArgAla Arg Glu Arg Asn Thr Arg Met Gly Glu 1010 1015 1020 Pro Glu Gly HisGlu Glu Pro Arg Gly Ala Glu Glu Ser Ile Ser 1025 1030 1035 Ala Leu GlyAsp Leu Phe Ala Asp Leu Lys Phe Ala Leu Ser Glu 1040 1045 1050 Glu AspPro Trp Lys Ala Phe Glu Phe Leu Lys His Ala Trp Lys 1055 1060 1065 IleAla Gly Lys Ile Arg Leu Lys Pro Thr Cys Ser Phe 1070 1075 1080 52 7080DNA Arabidopsis thaliana 52 ctcttcgccg actgtttcac tccccttctc tctcactctctgtgcgcttt attccactct 60 ccgatggctc cgtctcgccg acagatcagc ggaagatctccgttggtgaa ccagcagcgt 120 caaatcacct ccttctttgg gaaatctgct tcatcatcttcttctccgtc tccatctcct 180 tcaccatctc tctccaataa gaaaaccccc aaatctaacaaccctaaccc taaatctccg 240 tctccgtcac catctccgcc taagaaaacc cccaaattgaaccctaaccc tagttctaat 300 cttcctgctc gtagtcctag ccctggtcct gatactccttctcctgtaca gtccaagttt 360 aagaagcccc ttctcgtcat cggacagaca ccttcgcctcctcaatcggt ggtaattact 420 tacggtgacg aggtggtggg gaagcaagtt agggtttattggcctttgga taaaaaatgg 480 tatgatggga gcgtgacgtt ttatgataag ggtgagggtaagcatgtggt tgagtatgaa 540 gatggggaag aagagtcttt ggatttggga aaggagaagactgagtgggt ggttggggaa 600 aaatcaggag ataggtttaa tcgattgaaa cgaggcgcttcggctttgag aaaagttgtg 660 acggatagtg atgatgatgt ggagatgggt aatgtggaagaagataaaag tgacggtgat 720 gattctagcg atgaggattg gggaaagaat gttgggaaggaggtttgtga gagtgaagaa 780 gatgatgtgg agttggttga tgagaatgaa atggatgaagaagagttggt ggaagagaaa 840 gatgaagaaa cttctaaagt taatagagta tccaaaactgactctagaaa gcggaagact 900 agtgaagtaa cgaaatcagg tggtgagaag aaaagcaagactgatacagg cactatcttg 960 aaaggtttta aggcttctgt tgtggagcct gcgaagaagattggacaagg taaaccgaag 1020 agtctcttgt tgtaatcata tgcttgtatt tgcattgttttagtttgtgg tatgtctctt 1080 gcactgactt ttgtttcaga tagtgtatgt tgttggttgcttaatattat ttgtgtctta 1140 ctacagctga tagggtggtc aagggtttgg aagataacgtgttggatggg gatgctcttg 1200 ctagatttgg tgctcgtgat tctgagaaat tccgctttttgggagtgtaa gtctttcaca 1260 aaaaaaattc catcttagag gctatttgct acggtggttaggagtagaga atgtaaattt 1320 gtgtcttaag caatattgac ttctctactg gcaggagcatctctggtttt cttttatctt 1380 catgatgtat tagtaggctg catgatccct attctagctaagttagttct gttaattatt 1440 tttggtgaac agagaccgaa gggatgctaa aaggagacgccctactgatg agaattatga 1500 tccgaggaca ctctacctcc ctcctgattt tgtgaaaaaattaactggag gccaggtcag 1560 aagagcgcat ggaaatctgg ttcaggattt ttggtgaagctaatcaactt tcacttatat 1620 gattttgtgg ccttttttca gagacaatgg tgggagtttaaagcaaagca tatggacaaa 1680 gttgtattct tcaaggtaga acgataatta cttatttcgttataacttat ttattgatgg 1740 gagattctag gataaatggt cttcttttgt ggcaagcagatgggtaaatt ctatgagctt 1800 tttgagatgg atgcacatgt cggagctaag gaactggatatacaatacat gaaggtaact 1860 gtttgttatg actcataact aggtgatgca tttgaagacatctgttaaaa atgttaaaaa 1920 accgaaaatt tggcatcaga ttatgctaaa agggttcttttcattggtgt tacattacaa 1980 atttctcctg tattgtctct aatgtatctc tctttacaagcccctgacat atgcatttat 2040 tttgtaggga gagcaacctc attgtggatt tccggagaagaatttttctg taaacattga 2100 gaaattagtt agaaaggttt gtttccagaa atatagcaactccagttcaa gcgtgatcta 2160 tttcttgtta cgtgtagaga aattacattc atggcaaatgctgtactttg ggtagaaata 2220 aagttgattg aattgaatgg aacagggcta tcgggttttagttgtcgaac aaacagaaac 2280 acctgatcag ctggagcaac gccgaaaaga gacaggttccaaggataaag tatgtcccac 2340 tatgaatcta atttagttgg cattatcagt tcaagtcaatttgtttgctc ttgaaactaa 2400 aatttgttca ctttgggtga tgcctatgta gaaaaattatgatagggagg gctcatagtg 2460 acagaacttc tgtttttata ggttgtgaag cgcgaagtatgtgcagttgt tacaaaaggc 2520 acgctgacag atggggagat gctattaact aatccggatgcatcttatct aatggccttg 2580 actgaaggag gagaaagttt aactaatcct acagcagagcacaattttgg tgtatgtttg 2640 gttgatgttg cgacacagaa gataatactg ggccaggtgagttctagttg atgaatggta 2700 cctggttgca cttatacgta acatttctcg gtgtatattgatggcatttt tttttcattc 2760 gtaccagttt aaggatgatc aagattgcag tgcattatcttgcctgctat ctgagatgag 2820 gccggtggaa attattaaac cagctaaggt gttgagttatgcaacagaga gaacaatagt 2880 tagacaaacc agaaatccct tagtaaataa tctcgttccactttctgaat tttgggattc 2940 ggagaagacc atatatgaag ttggaattat ctacaagcgaatcaattgtc aaccgtcttc 3000 tgcttattct agtgagggaa agattctagg tgatggttcaagctttcttc caaaaatgtt 3060 gtctgaatta gcaactgaag ataagaatgg tagcctggcactctctgctc ttggtggtgc 3120 catttactac ctgcgacaag cattcttgga tgagagtctgcttagatttg caaagtttga 3180 atccctgcct tactgtgatt tcagcaacgt taatgagaagcagcacatgg ttcttgatgc 3240 tgctgctctt gaaaaccttg agatatttga aaacagtagaaatggaggct attcagggta 3300 aagtttctct atcttaccat gtattattaa acataattgatgtgttctaa atctagagtg 3360 ttgtcttttg aagaacgctg tatgctcaac tgaatcaatgtatcactgca tctgggaaac 3420 ggttactgaa aacatggctg gcaagacctt tatataatacggaactgatc aaggaacgac 3480 aagatgctgt agcaattctg cgggtgagtc tttcaacaagttgtttgact ttgctgctgt 3540 catttctctg tctctcaact agacaataac ttggcatcttggtttcacat ttgatcattt 3600 ttcatgtctg tttcgctatc catggatctc tcctcagaattacactattt ccccattatg 3660 ggtgttcaag accatttttg ccactgtttc actggcaaagatgatgtttt cctatgcgtt 3720 caactaacca tctatttcta gaacttattc cctaagattataaaacttac tctgcttctt 3780 cagcatgtca aggctttcgt ttacactatc catctgacaatgtattatgg tactgtccct 3840 tccctcaggg tgaaaatctt ccgtactcac tggaattccggaagtcgttg tccagacttc 3900 cagacatgga acggttgatt gcacgtatgt tttctagcatgtaagggatt agctagattg 3960 agatgttaat tcttacatta tatgtttata ccaaagacttactaaacata tttgttaaac 4020 ttgtgttacg tgttatagtg aagctagtgg aagaaatggcgataaagtgg tgctatatga 4080 agatacagct aagaagcagg tacaggaatt catatcaactctacgtggtt gtgaaacaat 4140 ggcagaagca tgctcttctc tccgtgctat cttgaagcatgatacatcca ggcggctgct 4200 tcatttacta actcctggta taatcaattt gctccatattcacattctta tactggcaaa 4260 ttgcacagca tctcatatca tttctctgcc aggtcaaagtcttccaaata tatcatcctc 4320 cataaagtat ttcaaggatg cttttgactg ggtagaagctcacaattctg gacgtgtaat 4380 accccatgaa ggagcagatg aagagtatga ttgtgcctgcaaaacagtag aagaatttga 4440 gtccagtttg aaaaaacatc tgaaagagca acggaaattactcggagatg catcagtgag 4500 aattacttca ctattttttt ttactcctta aatggctaatcaaccgaggg ttttctgatc 4560 agatctttgg tgctcttttg tcttcttatc cagataaactatgttacagt tggaaaagat 4620 gaatacctct tggaagttcc tgaaagttta agtgggagtgttcctcatga ttatgaatta 4680 tgctcatcga aaaaggtaaa agttgtacca agtttcacattctaaagaaa ttggcatttc 4740 gctttcgtca taacaagtcg atagtcttct cgtaattgctgtctgctgat atatttacta 4800 tatagagacc cttaatttta aacatgagat tttcttactttttactctct ttcagggtgt 4860 ctctcgatat tggactccta ccataaagaa attattaaaagagctatcac aagcaaaatc 4920 tgaaaaagag tcggccctga agagcatttc acagagattgattggacgtt tctgcgagca 4980 tcaagaaaaa tggagacaat tggtttctgc aacagctggtatggacaagt tcatgtttta 5040 aaaaaaaaaa attgtttaag gaattttcag catcttccttcagaatatgt atcttgctta 5100 tccaattcct gttaattact gtcacccagt gttagctttgtgggtcgtcg cttggaccct 5160 tttcgttgtg aacatttgtt gagctagtta gaattgagtttgatcccaca ctttatagat 5220 tgagttagaa gtaggcatgc agaagaaaat gaatcttaggcagacgtata gttcaatcac 5280 atcttataag caagaggttt cttgggtgga agattgttttatagaattag gcatgcaaac 5340 aactttgcac ttagaccttt atgtggatac atttttgacatgaattcttt ctattgcaga 5400 gctggacgtg ttgatcagcc tcgcttttgc aagtgattcttatgaaggag taagatgccg 5460 cccagtaata tctggttcta catctgatgg tgttccacacttgtctgcca ctggtctagg 5520 gcatccagtt ctaaggggtg attcgttagg cagaggctcttttgtaccaa ataatgtaaa 5580 gataggtggt gctgagaaag ccagtttcat cctcctcacaggccctaata tgggtggaaa 5640 atcaaccctt cttcgccaag tttgcttggc tgtaatcttggctcaggtaa gctatcattt 5700 gaaaaaactt tgtaggcaat gggctttgac ccgtttaattttgatgaaag aaactcaagc 5760 aatgatgatc ttttcacaga ttggagcaga tgtcccagcagaaacctttg aggtttcgcc 5820 tgttgacaaa atttgtgtcc ggatgggtgc aaaagatcatatcatggcag gacaaagcac 5880 gtttttaaca gaactttcag aaactgcggt aatgttggtaagtaatgttc attctgtttg 5940 tcaaattgat tacatgaagc tttctaagat aaatgtgaaacttgccacag tggttaccct 6000 tttgagagtt ggtcacaggc tttgttaaac tatgcgaatgccaacaaacg cactgataga 6060 atgttttata ttaataatat gcagacatca gccacccgaaactcgctggt ggtgctagat 6120 gagcttggac gaggaacagc cacatcagat gggcaagccattgcgtatgt tgaatcaatt 6180 attgcgtatc atgttttttg ggacttactg ttattgttcactttatctaa aatatcttaa 6240 ctatttacag ggaatccgta cttgagcact tcatagaaaaggtgcagtgt agaggattct 6300 tctctactca ttatcatcgt ctctctgtgg attatcaaaccaatccaaag gtattgtgaa 6360 aagtgtctgc ttcagtttct gggtttgaaa gacttgagaactatcaataa taatctgatt 6420 gtttgtgtac attctgaaac ttgtcaaaaa ccgatcagtcttgaatattt gtttggatag 6480 gtctcacttt gccatatggc atgtcaaata ggagaaggaatcggtggagt agaagaagtt 6540 acatttctct atagattgac tcctggtgca tgtcctaaaagttatggagt taacgttgct 6600 cggttagctg gtaagaacac tgaattctct actccatcacctctactcag ttaaacagaa 6660 gcagtcactc atcaaattgt tttggtttta atctccataggtcttccaga ttacgtactc 6720 cagagagccg tgataaaatc ccaagaattc gaggctttgtacggtaaaaa ccatagaaaa 6780 accgatcata aattagcagc aatgataaag cagatcatcagcagtgttgc atcagattct 6840 gattactcag cttcaaagga ctcattgtgt gagctacactccatggccaa tacatttctc 6900 cggttaacca actaatttaa cagctctacg cctttccggtttgtcgttct tcttgtaact 6960 ctttaaccaa ggtcaatcca cgagcttcgt cgtgtcaaatactaaaacct gagtcagcct 7020 gaaactaaac tcctgagtag agactcagtt ttgaggtgtgggtttagctt ctgagtcttt 7080 53 1324 PRT Arabidopsis thaliana 53 Met AlaPro Ser Arg Arg Gln Ile Ser Gly Arg Ser Pro Leu Val Asn 1 5 10 15 GlnGln Arg Gln Ile Thr Ser Phe Phe Gly Lys Ser Ala Ser Ser Ser 20 25 30 SerSer Pro Ser Pro Ser Pro Ser Pro Ser Leu Ser Asn Lys Lys Thr 35 40 45 ProLys Ser Asn Asn Pro Asn Pro Lys Ser Pro Ser Pro Ser Pro Ser 50 55 60 ProPro Lys Lys Thr Pro Lys Leu Asn Pro Asn Pro Ser Ser Asn Leu 65 70 75 80Pro Ala Arg Ser Pro Ser Pro Gly Pro Asp Thr Pro Ser Pro Val Gln 85 90 95Ser Lys Phe Lys Lys Pro Leu Leu Val Ile Gly Gln Thr Pro Ser Pro 100 105110 Pro Gln Ser Val Val Ile Thr Tyr Gly Asp Glu Val Val Gly Lys Gln 115120 125 Val Arg Val Tyr Trp Pro Leu Asp Lys Lys Trp Tyr Asp Gly Ser Val130 135 140 Thr Phe Tyr Asp Lys Gly Glu Gly Lys His Val Val Glu Tyr GluAsp 145 150 155 160 Gly Glu Glu Glu Ser Leu Asp Leu Gly Lys Glu Lys ThrGlu Trp Val 165 170 175 Val Gly Glu Lys Ser Gly Asp Arg Phe Asn Arg LeuLys Arg Gly Ala 180 185 190 Ser Ala Leu Arg Lys Val Val Thr Asp Ser AspAsp Asp Val Glu Met 195 200 205 Gly Asn Val Glu Glu Asp Lys Ser Asp GlyAsp Asp Ser Ser Asp Glu 210 215 220 Asp Trp Gly Lys Asn Val Gly Lys GluVal Cys Glu Ser Glu Glu Asp 225 230 235 240 Asp Val Glu Leu Val Asp GluAsn Glu Met Asp Glu Glu Glu Leu Val 245 250 255 Glu Glu Lys Asp Glu GluThr Ser Lys Val Asn Arg Val Ser Lys Thr 260 265 270 Asp Ser Arg Lys ArgLys Thr Ser Glu Val Thr Lys Ser Gly Gly Glu 275 280 285 Lys Lys Ser LysThr Asp Thr Gly Thr Ile Leu Lys Gly Phe Lys Ala 290 295 300 Ser Val ValGlu Pro Ala Lys Lys Ile Gly Gln Ala Asp Arg Val Val 305 310 315 320 LysGly Leu Glu Asp Asn Val Leu Asp Gly Asp Ala Leu Ala Arg Phe 325 330 335Gly Ala Arg Asp Ser Glu Lys Phe Arg Phe Leu Gly Val Asp Arg Arg 340 345350 Asp Ala Lys Arg Arg Arg Pro Thr Asp Glu Asn Tyr Asp Pro Arg Thr 355360 365 Leu Tyr Leu Pro Pro Asp Phe Val Lys Lys Leu Thr Gly Gly Gln Arg370 375 380 Gln Trp Trp Glu Phe Lys Ala Lys His Met Asp Lys Val Val PhePhe 385 390 395 400 Lys Met Gly Lys Phe Tyr Glu Leu Phe Glu Met Asp AlaHis Val Gly 405 410 415 Ala Lys Glu Leu Asp Ile Gln Tyr Met Lys Gly GluGln Pro His Cys 420 425 430 Gly Phe Pro Glu Lys Asn Phe Ser Val Asn IleGlu Lys Leu Val Arg 435 440 445 Lys Gly Tyr Arg Val Leu Val Val Glu GlnThr Glu Thr Pro Asp Gln 450 455 460 Leu Glu Gln Arg Arg Lys Glu Thr GlySer Lys Asp Lys Val Val Lys 465 470 475 480 Arg Glu Val Cys Ala Val ValThr Lys Gly Thr Leu Thr Asp Gly Glu 485 490 495 Met Leu Leu Thr Asn ProAsp Ala Ser Tyr Leu Met Ala Leu Thr Glu 500 505 510 Gly Gly Glu Ser LeuThr Asn Pro Thr Ala Glu His Asn Phe Gly Val 515 520 525 Cys Leu Val AspVal Ala Thr Gln Lys Ile Ile Leu Gly Gln Phe Lys 530 535 540 Asp Asp GlnAsp Cys Ser Ala Leu Ser Cys Leu Leu Ser Glu Met Arg 545 550 555 560 ProVal Glu Ile Ile Lys Pro Ala Lys Val Leu Ser Tyr Ala Thr Glu 565 570 575Arg Thr Ile Val Arg Gln Thr Arg Asn Pro Leu Val Asn Asn Leu Val 580 585590 Pro Leu Ser Glu Phe Trp Asp Ser Glu Lys Thr Ile Tyr Glu Val Gly 595600 605 Ile Ile Tyr Lys Arg Ile Asn Cys Gln Pro Ser Ser Ala Tyr Ser Ser610 615 620 Glu Gly Lys Ile Leu Gly Asp Gly Ser Ser Phe Leu Pro Lys MetLeu 625 630 635 640 Ser Glu Leu Ala Thr Glu Asp Lys Asn Gly Ser Leu AlaLeu Ser Ala 645 650 655 Leu Gly Gly Ala Ile Tyr Tyr Leu Arg Gln Ala PheLeu Asp Glu Ser 660 665 670 Leu Leu Arg Phe Ala Lys Phe Glu Ser Leu ProTyr Cys Asp Phe Ser 675 680 685 Asn Val Asn Glu Lys Gln His Met Val LeuAsp Ala Ala Ala Leu Glu 690 695 700 Asn Leu Glu Ile Phe Glu Asn Ser ArgAsn Gly Gly Tyr Ser Gly Thr 705 710 715 720 Leu Tyr Ala Gln Leu Asn GlnCys Ile Thr Ala Ser Gly Lys Arg Leu 725 730 735 Leu Lys Thr Trp Leu AlaArg Pro Leu Tyr Asn Thr Glu Leu Ile Lys 740 745 750 Glu Arg Gln Asp AlaVal Ala Ile Leu Arg Gly Glu Asn Leu Pro Tyr 755 760 765 Ser Leu Glu PheArg Lys Ser Leu Ser Arg Leu Pro Asp Met Glu Arg 770 775 780 Leu Ile AlaArg Met Phe Ser Ser Ile Glu Ala Ser Gly Arg Asn Gly 785 790 795 800 AspLys Val Val Leu Tyr Glu Asp Thr Ala Lys Lys Gln Val Gln Glu 805 810 815Phe Ile Ser Thr Leu Arg Gly Cys Glu Thr Met Ala Glu Ala Cys Ser 820 825830 Ser Leu Arg Ala Ile Leu Lys His Asp Thr Ser Arg Arg Leu Leu His 835840 845 Leu Leu Thr Pro Gly Gln Ser Leu Pro Asn Ile Ser Ser Ser Ile Lys850 855 860 Tyr Phe Lys Asp Ala Phe Asp Trp Val Glu Ala His Asn Ser GlyArg 865 870 875 880 Val Ile Pro His Glu Gly Ala Asp Glu Glu Tyr Asp CysAla Cys Lys 885 890 895 Thr Val Glu Glu Phe Glu Ser Ser Leu Lys Lys HisLeu Lys Glu Gln 900 905 910 Arg Lys Leu Leu Gly Asp Ala Ser Ile Asn TyrVal Thr Val Gly Lys 915 920 925 Asp Glu Tyr Leu Leu Glu Val Pro Glu SerLeu Ser Gly Ser Val Pro 930 935 940 His Asp Tyr Glu Leu Cys Ser Ser LysLys Gly Val Ser Arg Tyr Trp 945 950 955 960 Thr Pro Thr Ile Lys Lys LeuLeu Lys Glu Leu Ser Gln Ala Lys Ser 965 970 975 Glu Lys Glu Ser Ala LeuLys Ser Ile Ser Gln Arg Leu Ile Gly Arg 980 985 990 Phe Cys Glu His GlnGlu Lys Trp Arg Gln Leu Val Ser Ala Thr Ala 995 1000 1005 Glu Leu AspVal Leu Ile Ser Leu Ala Phe Ala Ser Asp Ser Tyr 1010 1015 1020 Glu GlyVal Arg Cys Arg Pro Val Ile Ser Gly Ser Thr Ser Asp 1025 1030 1035 GlyVal Pro His Leu Ser Ala Thr Gly Leu Gly His Pro Val Leu 1040 1045 1050Arg Gly Asp Ser Leu Gly Arg Gly Ser Phe Val Pro Asn Asn Val 1055 10601065 Lys Ile Gly Gly Ala Glu Lys Ala Ser Phe Ile Leu Leu Thr Gly 10701075 1080 Pro Asn Met Gly Gly Lys Ser Thr Leu Leu Arg Gln Val Cys Leu1085 1090 1095 Ala Val Ile Leu Ala Gln Ile Gly Ala Asp Val Pro Ala GluThr 1100 1105 1110 Phe Glu Val Ser Pro Val Asp Lys Ile Cys Val Arg MetGly Ala 1115 1120 1125 Lys Asp His Ile Met Ala Gly Gln Ser Thr Phe LeuThr Glu Leu 1130 1135 1140 Ser Glu Thr Ala Val Met Leu Thr Ser Ala ThrArg Asn Ser Leu 1145 1150 1155 Val Val Leu Asp Glu Leu Gly Arg Gly ThrAla Thr Ser Asp Gly 1160 1165 1170 Gln Ala Ile Ala Glu Ser Val Leu GluHis Phe Ile Glu Lys Val 1175 1180 1185 Gln Cys Arg Gly Phe Phe Ser ThrHis Tyr His Arg Leu Ser Val 1190 1195 1200 Asp Tyr Gln Thr Asn Pro LysVal Ser Leu Cys His Met Ala Cys 1205 1210 1215 Gln Ile Gly Glu Gly IleGly Gly Val Glu Glu Val Thr Phe Leu 1220 1225 1230 Tyr Arg Leu Thr ProGly Ala Cys Pro Lys Ser Tyr Gly Val Asn 1235 1240 1245 Val Ala Arg LeuAla Gly Leu Pro Asp Tyr Val Leu Gln Arg Ala 1250 1255 1260 Val Ile LysSer Gln Glu Phe Glu Ala Leu Tyr Gly Lys Asn His 1265 1270 1275 Arg LysThr Asp His Lys Leu Ala Ala Met Ile Lys Gln Ile Ile 1280 1285 1290 SerSer Val Ala Ser Asp Ser Asp Tyr Ser Ala Ser Lys Asp Ser 1295 1300 1305Leu Cys Glu Leu His Ser Met Ala Asn Thr Phe Leu Arg Leu Thr 1310 13151320 Asn 54 2340 DNA Arabidopsis thaliana 54 atgcaaggag attcttctccgtctccgacg actactagct ctcctttgat aagacctata 60 aacagaaacg taattcacagaatctgttcc ggtcaagtca tcttagacct ctcttcggcc 120 gtcaaggagc ttgtcgagaatagtctcgac gccggcgcca ccagtataga gattaacctc 180 cgagactacg gcgaagactattttcaggtc attgacaatg gttgtggcat ttccccaacc 240 aatttcaagg tttgtgtccaaattctccga agaacttttg atgttcttgc acttaagcat 300 catacttcta aattagaggatttcacagat cttttgaatt tgactactta tggttttaga 360 ggagaagcct tgagctctctctgtgcattg ggaaatctca ctgtggaaac aagaacaaag 420 aatgagccag ttgctacgctcttgacgttt gatcattctg gtttgcttac tgctgaaaag 480 aagactgctc gccaaattggtaccactgtc actgttagga agttgttctc taatttacct 540 gtacgaagca aagagtttaagcggaatata cgcaaagaat atgggaagct tgtatcttta 600 ttgaacgcat atgcgcttattgcgaaagga gtgcggtttg tctgctctaa cacgactggg 660 aaaaacccaa agtctgttgtgctgaacaca caagggaggg gttcacttaa agataatatc 720 ataacagttt tcggcattagtacctttaca agtctacagc ctggtactgg acgcaattta 780 gcagatcgac agtatttctttataaatggt cggcctgtag atatgccaaa agtcagcaag 840 ttggtgaatg agttatataaagatacaagt tctcggaaat atccagttac cattctggat 900 tttattgtgc ctggtggagcatgtgatttg aatgtcacgc ccgataaaag aaaggtgttc 960 ttttctgacg agacttctgttatcggttct ttgagggaag gtctgaacga gatatattcc 1020 tccagtaatg cgtcttatattgttaatagg ttcgaggaga attcggagca accagataag 1080 gctggagttt cgtcgtttcagaagaaatca aatcttttgt cagaagggat agttctggat 1140 gtcagttcta aaacaagactaggggaagct attgagaaag aaaatccatc cttaagggag 1200 gttgaaattg ataatagttcgccaatggag aagtttaagt ttgagatcaa ggcatgtggg 1260 acgaagaaag gggaaggttctttatcagtc catgatgtaa ctcaccttga caagacacct 1320 agcaaaggtt tgcctcagttaaatgtgact gagaaagtta ctgatgcaag taaagacttg 1380 agcagccgct ctagctttgcccagtcaact ttgaatactt ttgttaccat gggaaaaaga 1440 aaacatgaaa acataagcaccatcctctct gaaacacctg tcctcagaaa ccaaacttct 1500 agttatcgtg tggagaaaagcaaatttgaa gttcgtgcct tagcttcaag gtgtctcgtg 1560 gaaggcgatc aacttgatgatatggtcatc tcaaaggaag atatgacacc aagcgaaaga 1620 gattctgaac taggcaatcggatttctcct ggaacacaag ctgataatgt tgaaagacat 1680 gagagagtac tcgggcaattcaatcttggg ttcatcattg caaaattgga gcgagatctg 1740 ttcattgtgg atcagcatgcagctgatgag aaattcaact tcgaacattt agcaaggtca 1800 actgtcctga accagcaacccttactccag cctttgaact tggaactctc tccagaagaa 1860 gaagtaactg tgttaatgcacatggatatt atcagggaaa atggctttct tctagaggag 1920 aatccaagtg ctcctcccggaaaacacttt agactacgag ccattcctta tagcaagaat 1980 atcacctttg gagtcgaagatcttaaagac ctgatctcaa ctctaggaga taaccatggg 2040 gaatgttcgg ttgctagtagctacaaaacc agcaaaacag attcgatttg tccatcacga 2100 gtccgtgcaa tgctagcatcccgagcatgc agatcatctg tgatgatcgg agatccactc 2160 agaaaaaacg aaatgcagaagatagtagaa cacttggcag atctcgaatc tccttggaat 2220 tgcccacacg gacgaccaacaatgcgtcat cttgtggact tgacaacttt actcacatta 2280 cctgatgacg acaatgtcaatgatgatgat gatgatgatg caaccatctc attggcatga 2340 55 779 PRT Arabidopsisthaliana 55 Met Gln Gly Asp Ser Ser Pro Ser Pro Thr Thr Thr Ser Ser ProLeu 1 5 10 15 Ile Arg Pro Ile Asn Arg Asn Val Ile His Arg Ile Cys SerGly Gln 20 25 30 Val Ile Leu Asp Leu Ser Ser Ala Val Lys Glu Leu Val GluAsn Ser 35 40 45 Leu Asp Ala Gly Ala Thr Ser Ile Glu Ile Asn Leu Arg AspTyr Gly 50 55 60 Glu Asp Tyr Phe Gln Val Ile Asp Asn Gly Cys Gly Ile SerPro Thr 65 70 75 80 Asn Phe Lys Val Cys Val Gln Ile Leu Arg Arg Thr PheAsp Val Leu 85 90 95 Ala Leu Lys His His Thr Ser Lys Leu Glu Asp Phe ThrAsp Leu Leu 100 105 110 Asn Leu Thr Thr Tyr Gly Phe Arg Gly Glu Ala LeuSer Ser Leu Cys 115 120 125 Ala Leu Gly Asn Leu Thr Val Glu Thr Arg ThrLys Asn Glu Pro Val 130 135 140 Ala Thr Leu Leu Thr Phe Asp His Ser GlyLeu Leu Thr Ala Glu Lys 145 150 155 160 Lys Thr Ala Arg Gln Ile Gly ThrThr Val Thr Val Arg Lys Leu Phe 165 170 175 Ser Asn Leu Pro Val Arg SerLys Glu Phe Lys Arg Asn Ile Arg Lys 180 185 190 Glu Tyr Gly Lys Leu ValSer Leu Leu Asn Ala Tyr Ala Leu Ile Ala 195 200 205 Lys Gly Val Arg PheVal Cys Ser Asn Thr Thr Gly Lys Asn Pro Lys 210 215 220 Ser Val Val LeuAsn Thr Gln Gly Arg Gly Ser Leu Lys Asp Asn Ile 225 230 235 240 Ile ThrVal Phe Gly Ile Ser Thr Phe Thr Ser Leu Gln Pro Gly Thr 245 250 255 GlyArg Asn Leu Ala Asp Arg Gln Tyr Phe Phe Ile Asn Gly Arg Pro 260 265 270Val Asp Met Pro Lys Val Ser Lys Leu Val Asn Glu Leu Tyr Lys Asp 275 280285 Thr Ser Ser Arg Lys Tyr Pro Val Thr Ile Leu Asp Phe Ile Val Pro 290295 300 Gly Gly Ala Cys Asp Leu Asn Val Thr Pro Asp Lys Arg Lys Val Phe305 310 315 320 Phe Ser Asp Glu Thr Ser Val Ile Gly Ser Leu Arg Glu GlyLeu Asn 325 330 335 Glu Ile Tyr Ser Ser Ser Asn Ala Ser Tyr Ile Val AsnArg Phe Glu 340 345 350 Glu Asn Ser Glu Gln Pro Asp Lys Ala Gly Val SerSer Phe Gln Lys 355 360 365 Lys Ser Asn Leu Leu Ser Glu Gly Ile Val LeuAsp Val Ser Ser Lys 370 375 380 Thr Arg Leu Gly Glu Ala Ile Glu Lys GluAsn Pro Ser Leu Arg Glu 385 390 395 400 Val Glu Ile Asp Asn Ser Ser ProMet Glu Lys Phe Lys Phe Glu Ile 405 410 415 Lys Ala Cys Gly Thr Lys LysGly Glu Gly Ser Leu Ser Val His Asp 420 425 430 Val Thr His Leu Asp LysThr Pro Ser Lys Gly Leu Pro Gln Leu Asn 435 440 445 Val Thr Glu Lys ValThr Asp Ala Ser Lys Asp Leu Ser Ser Arg Ser 450 455 460 Ser Phe Ala GlnSer Thr Leu Asn Thr Phe Val Thr Met Gly Lys Arg 465 470 475 480 Lys HisGlu Asn Ile Ser Thr Ile Leu Ser Glu Thr Pro Val Leu Arg 485 490 495 AsnGln Thr Ser Ser Tyr Arg Val Glu Lys Ser Lys Phe Glu Val Arg 500 505 510Ala Leu Ala Ser Arg Cys Leu Val Glu Gly Asp Gln Leu Asp Asp Met 515 520525 Val Ile Ser Lys Glu Asp Met Thr Pro Ser Glu Arg Asp Ser Glu Leu 530535 540 Gly Asn Arg Ile Ser Pro Gly Thr Gln Ala Asp Asn Val Glu Arg His545 550 555 560 Glu Arg Val Leu Gly Gln Phe Asn Leu Gly Phe Ile Ile AlaLys Leu 565 570 575 Glu Arg Asp Leu Phe Ile Val Asp Gln His Ala Ala AspGlu Lys Phe 580 585 590 Asn Phe Glu His Leu Ala Arg Ser Thr Val Leu AsnGln Gln Pro Leu 595 600 605 Leu Gln Pro Leu Asn Leu Glu Leu Ser Pro GluGlu Glu Val Thr Val 610 615 620 Leu Met His Met Asp Ile Ile Arg Glu AsnGly Phe Leu Leu Glu Glu 625 630 635 640 Asn Pro Ser Ala Pro Pro Gly LysHis Phe Arg Leu Arg Ala Ile Pro 645 650 655 Tyr Ser Lys Asn Ile Thr PheGly Val Glu Asp Leu Lys Asp Leu Ile 660 665 670 Ser Thr Leu Gly Asp AsnHis Gly Glu Cys Ser Val Ala Ser Ser Tyr 675 680 685 Lys Thr Ser Lys ThrAsp Ser Ile Cys Pro Ser Arg Val Arg Ala Met 690 695 700 Leu Ala Ser ArgAla Cys Arg Ser Ser Val Met Ile Gly Asp Pro Leu 705 710 715 720 Arg LysAsn Glu Met Gln Lys Ile Val Glu His Leu Ala Asp Leu Glu 725 730 735 SerPro Trp Asn Cys Pro His Gly Arg Pro Thr Met Arg His Leu Val 740 745 750Asp Leu Thr Thr Leu Leu Thr Leu Pro Asp Asp Asp Asn Val Asn Asp 755 760765 Asp Asp Asp Asp Asp Ala Thr Ile Ser Leu Ala 770 775 56 440 DNAArabidopsis thaliana 56 atgcaaggag attcttctcc gtctccgacg actactagctctcctttgat aagacctata 60 aacagaaacg taattcacag aatctcttcc ggtcaagtcatcttagacct ctcttcggcc 120 gtcaaggagc ttgtcgagaa tagtctcgac gcggcgccaccagtatagag attaacctcc 180 gagactacgg cgaagactat tttcaggtca ttgacaatggttgtggcatt tccccaacca 240 atttcaaggt ttgtgtccaa attctccgaa gaacttttgatgttcttgca cttaagcatc 300 atacttctaa attagaggat ttcacagatc ttttgaatttgactacttat ggttttagag 360 gagaagcctt gagctctctc tgtgcattgg gaaatctcactgtggaaaca agaacaaaga 420 atgagccagt tgctacgctc 440 57 141 PRTArabidopsis thaliana 57 Met Gln Gly Asp Ser Ser Pro Ser Pro Thr Thr ThrSer Ser Pro Leu 1 5 10 15 Ile Arg Pro Ile Asn Arg Asn Val Ile His ArgIle Ser Ser Gly Gln 20 25 30 Val Ile Leu Asp Leu Ser Ser Ala Val Lys GluLeu Val Glu Asn Ser 35 40 45 Leu Asp Ala Ala Pro Pro Val Arg Leu Thr SerGlu Thr Thr Ala Lys 50 55 60 Thr Ile Phe Arg Ser Leu Thr Met Val Val AlaPhe Pro Gln Pro Ile 65 70 75 80 Ser Arg Phe Val Ser Lys Phe Ser Glu GluLeu Leu Met Phe Leu His 85 90 95 Leu Ser Ile Ile Leu Leu Asn Arg Ile SerGln Ile Phe Ile Leu Leu 100 105 110 Met Val Leu Glu Glu Lys Pro Ala LeuSer Val His Trp Glu Ile Ser 115 120 125 Leu Trp Lys Gln Glu Gln Arg MetSer Gln Leu Leu Arg 130 135 140 58 2501 DNA Oryza sativa 58 cggcacgagattttgcagtc tcctctcctc ctccgctcga gcgagtgagt cccgaccacg 60 tcgctgccctcgcctcaccg ccggccaacc gccgtgacga gagatcgagc agggcggggc 120 atggacgagccttcgccgcg cggaggtggg tgcgccgggg agccgccccg catccggagg 180 ttggaggagtcggtggtgaa ccgcatcgcg gcgggggagg tgatccagcg gccgtcgtcg 240 gcggtgaaggagctcatcga gaacagcctc gacgctggcg cctccagcgt ctccgttgcg 300 gtgaaggacggtggcctcaa gctcatccag gtctccgatg acggccatgg catcaggttt 360 gaggatttggcaatattgtg cgaaaggcat actacctcaa agttatctgc atacgaggat 420 ctgcagaccataaaatcgat ggggttcaga ggggaggctt tggctagtat gacttatgtt 480 ggccatgttaccgtgacaac gataacagaa ggccaattgc acggctacag ggtttcttac 540 agagatggtgtaatggagaa tgagcctaag ccttgcgctg cggtgaaagg aactcaagtc 600 atggttgaaaatctatttta caacatggta gcccgcaaga aaacattgca gaactccaat 660 gatgactaccccaagatcgt agacttcatc agtcggtttg cagtccatca catcaacgtt 720 accttctcttgcagaaagca tggagccaat agagcagatg ttcatagtgc aagtacatcc 780 tcaaggttagatgctatcag gagtgtctat ggggcttctg tcgttcgtga tctcatagaa 840 ataaaggtttcatatgagga tgctgcagat tcaatcttca agatggatgg ttacatctca 900 aatgcaaattatgtggcaaa gaagattaca atgattcttt tcataaatga taggcttgta 960 gactgtactgctttgaaaag agctattgaa tttgtgtact ctgcaacatt gcctcaagca 1020 tccaaacctttcatatacat gtccatacat cttccatcag aacacgtgga tgttaatata 1080 cacccaaccaagaaagaggt tagccttttg aatcaagagc gtattattga aacaataaga 1140 aatgctattgaggaaaaact gatgaattct aatacaacca ggatattcca aactcaggca 1200 ttaaacttatcagggattgc tcaagctaac ccacaaaagg ataaggtttc tgaggccagt 1260 atgggttctggaacaaaatc tcaaaaaatt cctgtgagcc aaatggtcag aacagatcca 1320 cgcaatccatctggaagatt gcacacctac tggcacgggc aatcttcaaa tcttgaaaag 1380 aaatttgatcttgtatctgt aagaaatgtt gtaagatcaa ggagaaacca aaaagatgct 1440 ggtgatttgtcaagccgtca tgagctcctt gtggaaatag attctagctt ccatcctggc 1500 cttttggacattgtcaagaa ctgcacatat gttggacttg ccgatgaagc ctttgctttg 1560 atacaacacaatacccgctt ataccttgta aatgtggtaa atattagtaa agaacttatg 1620 taccagcaagctttgtgccg ttttgggaac ttcaatgcta ttcagctcag tgaaccagct 1680 ccacttcaggagttgctggt gatggcactg aaagacgatg aattgatgag tgatgaaaag 1740 gatgatgagaaactggagat tgcagaagta aacactgaga tactaaaaga aaatgctgag 1800 atgattaatgagtacttttc tattcacatt gatcaagatg gcaaattgac aagacttcct 1860 gttgtactggaccagtacac ccctgatatg gaccgtcttc cagaatttgt gttggcttta 1920 ggaaatgatgttacttggga tgacgagaaa gagtgcttca gaacagtagc ttctgctgta 1980 ggaaacttctatgcacttca tcccccaatc cttccaaatc catctgggaa tggcattcat 2040 ttatacaagaaaaatagaga ttcaatggct gatgaacatg ctgagaatga tctaatatca 2100 gatgaaaatgacgttgatca agaacttctt gcggaagcag aagcagcatg ggcccaacgt 2160 gagtggaccattcagcatgt cttgtttcca tccatgcgac ttttcctcaa gcccccgaag 2220 tcaatggcaacagatggaac gtttgtgcag gttgcttcct tggagaaact ctacaagatt 2280 tttgaaaggtgttagctcat aagtgagaaa atgaaggcag agtaagatca tgattcatgg 2340 agtgtttttgaaaatgtgta taatttcacc gtattatgta ctttgatagt gtctgtagaa 2400 actgaagaaagaaagatggc tttacttctg aattgaaagt taacgatgcc agcaattgta 2460 tattctgatcaaccaaaaaa aaaaaaaaaa aaaaaaaaaa a 2501 59 724 PRT Oryza sativa 59 MetAsp Glu Pro Ser Pro Arg Gly Gly Gly Cys Ala Gly Glu Pro Pro 1 5 10 15Arg Ile Arg Arg Leu Glu Glu Ser Val Val Asn Arg Ile Ala Ala Gly 20 25 30Glu Val Ile Gln Arg Pro Ser Ser Ala Val Lys Glu Leu Ile Glu Asn 35 40 45Ser Leu Asp Ala Gly Ala Ser Ser Val Ser Val Ala Val Lys Asp Gly 50 55 60Gly Leu Lys Leu Ile Gln Val Ser Asp Asp Gly His Gly Ile Arg Phe 65 70 7580 Glu Asp Leu Ala Ile Leu Cys Glu Arg His Thr Thr Ser Lys Leu Ser 85 9095 Ala Tyr Glu Asp Leu Gln Thr Ile Lys Ser Met Gly Phe Arg Gly Glu 100105 110 Ala Leu Ala Ser Met Thr Tyr Val Gly His Val Thr Val Thr Thr Ile115 120 125 Thr Glu Gly Gln Leu His Gly Tyr Arg Val Ser Tyr Arg Asp GlyVal 130 135 140 Met Glu Asn Glu Pro Lys Pro Cys Ala Ala Val Lys Gly ThrGln Val 145 150 155 160 Met Val Glu Asn Leu Phe Tyr Asn Met Val Ala ArgLys Lys Thr Leu 165 170 175 Gln Asn Ser Asn Asp Asp Tyr Pro Lys Ile ValAsp Phe Ile Ser Arg 180 185 190 Phe Ala Val His His Ile Asn Val Thr PheSer Cys Arg Lys His Gly 195 200 205 Ala Asn Arg Ala Asp Val His Ser AlaSer Thr Ser Ser Arg Leu Asp 210 215 220 Ala Ile Arg Ser Val Tyr Gly AlaSer Val Val Arg Asp Leu Ile Glu 225 230 235 240 Ile Lys Val Ser Tyr GluAsp Ala Ala Asp Ser Ile Phe Lys Met Asp 245 250 255 Gly Tyr Ile Ser AsnAla Asn Tyr Val Ala Lys Lys Ile Thr Met Ile 260 265 270 Leu Phe Ile AsnAsp Arg Leu Val Asp Cys Thr Ala Leu Lys Arg Ala 275 280 285 Ile Glu PheVal Tyr Ser Ala Thr Leu Pro Gln Ala Ser Lys Pro Phe 290 295 300 Ile TyrMet Ser Ile His Leu Pro Ser Glu His Val Asp Val Asn Ile 305 310 315 320His Pro Thr Lys Lys Glu Val Ser Leu Leu Asn Gln Glu Arg Ile Ile 325 330335 Glu Thr Ile Arg Asn Ala Ile Glu Glu Lys Leu Met Asn Ser Asn Thr 340345 350 Thr Arg Ile Phe Gln Thr Gln Ala Leu Asn Leu Ser Gly Ile Ala Gln355 360 365 Ala Asn Pro Gln Lys Asp Lys Val Ser Glu Ala Ser Met Gly SerGly 370 375 380 Thr Lys Ser Gln Lys Ile Pro Val Ser Gln Met Val Arg ThrAsp Pro 385 390 395 400 Arg Asn Pro Ser Gly Arg Leu His Thr Tyr Trp HisGly Gln Ser Ser 405 410 415 Asn Leu Glu Lys Lys Phe Asp Leu Val Ser ValArg Asn Val Val Arg 420 425 430 Ser Arg Arg Asn Gln Lys Asp Ala Gly AspLeu Ser Ser Arg His Glu 435 440 445 Leu Leu Val Glu Ile Asp Ser Ser PheHis Pro Gly Leu Leu Asp Ile 450 455 460 Val Lys Asn Cys Thr Tyr Val GlyLeu Ala Asp Glu Ala Phe Ala Leu 465 470 475 480 Ile Gln His Asn Thr ArgLeu Tyr Leu Val Asn Val Val Asn Ile Ser 485 490 495 Lys Glu Leu Met TyrGln Gln Ala Leu Cys Arg Phe Gly Asn Phe Asn 500 505 510 Ala Ile Gln LeuSer Glu Pro Ala Pro Leu Gln Glu Leu Leu Val Met 515 520 525 Ala Leu LysAsp Asp Glu Leu Met Ser Asp Glu Lys Asp Asp Glu Lys 530 535 540 Leu GluIle Ala Glu Val Asn Thr Glu Ile Leu Lys Glu Asn Ala Glu 545 550 555 560Met Ile Asn Glu Tyr Phe Ser Ile His Ile Asp Gln Asp Gly Lys Leu 565 570575 Thr Arg Leu Pro Val Val Leu Asp Gln Tyr Thr Pro Asp Met Asp Arg 580585 590 Leu Pro Glu Phe Val Leu Ala Leu Gly Asn Asp Val Thr Trp Asp Asp595 600 605 Glu Lys Glu Cys Phe Arg Thr Val Ala Ser Ala Val Gly Asn PheTyr 610 615 620 Ala Leu His Pro Pro Ile Leu Pro Asn Pro Ser Gly Asn GlyIle His 625 630 635 640 Leu Tyr Lys Lys Asn Arg Asp Ser Met Ala Asp GluHis Ala Glu Asn 645 650 655 Asp Leu Ile Ser Asp Glu Asn Asp Val Asp GlnGlu Leu Leu Ala Glu 660 665 670 Ala Glu Ala Ala Trp Ala Gln Arg Glu TrpThr Ile Gln His Val Leu 675 680 685 Phe Pro Ser Met Arg Leu Phe Leu LysPro Pro Lys Ser Met Ala Thr 690 695 700 Asp Gly Thr Phe Val Gln Val AlaSer Leu Glu Lys Leu Tyr Lys Ile 705 710 715 720 Phe Glu Arg Cys 60 287DNA Conyza sp. 60 cacatcttta gcatcggcca ccattgaaaa agtggctgaa tcatgggataaaaatgtcgc 60 tacaagtgtt gatgatggta gggacttgaa tgattctaat ggtgatggccttcactcgac 120 tgttgaacca acattgcgtg gtttgcatgc atatgttggt gattctaatgtacctccaaa 180 ccaaagttcc ctcctgatgc ttcttatttt caaccggctg catgtcatgcaaatgacatt 240 caccctgcta cagatgaggc ccctttgcat gatgtttctc cgaatga 28761 348 DNA Conyza sp. 61 atggtaggga tttgaatgat tcgactgggg atggcttacactcgactgct gaaccaacat 60 tgcatggttt gcatgcaaat gttgatgatt gtactgtgcctcctatgccg gaaccgccaa 120 agttccctcc tgatgctact tactttcagc cggctgcatgtcatgtaaat gacattcatc 180 ctgcttcaca tgaggcccct tatgcatgat gttactcctaatgatcttag tggataccct 240 gacagtccta aggtccagca gccgcgtact tatgcttctatctttcagga tgcggctaac 300 atcaacaaga aaggtaaatt gagattcatc cctccaaaaaaaaaaaaa 348 62 18 DNA Artificial Sequence Oligonucleotide primer 62cacatcttta gcatcggc 18 63 20 DNA Artificial Sequence Oligonucleotideprimer 63 tcattcggag aaacatcatg 20 64 52 DNA Artificial SequenceOligonucleotide primer 64 aagcagtggt atcaacgcag agtacttttt tttttttttttttttttttt vn 52 65 26 DNA Artificial Sequence Oligonucleotide primer 65cacatcttta gcatcggcca ccattg 26 66 45 DNA Artificial SequenceOligonucleotide primer 66 ctaatacgac tcactatagg gcaagcagtg gtatcaacgcagagt 45 67 22 DNA Artificial Sequence Oligonucleotide primer 67ctaatacgac tcactatagg gc 22 68 25 DNA Artificial SequenceOligonucleotide primer 68 gtggctgaat cgtggtataa gaatg 25 69 23 DNAArtificial Sequence Oligonucleotide primer 69 aagcagtggt atcaacgcag agt23 70 48 DNA Artificial Sequence Oligonucleotide primer 70 gtaatacgactcactatagg gcacgcgtgg tcgacggccc gggctggt 48 71 12 DNA ArtificialSequence Oligonucleotide primer 71 aattaccagc cc 12 72 12 DNA ArtificialSequence Oligonucleotide primer 72 gatcaccagc cc 12 73 12 DNA ArtificialSequence Oligonucleotide primer 73 agctaccagc cc 12 74 22 DNA ArtificialSequence Oligonucleotide primer 74 gtaatacgac tcactatagg gc 22 75 22 DNAArtificial Sequence Oligonucleotide primer 75 gagagagaga gagagagaga gb22 76 21 DNA Artificial Sequence Oligonucleotide primer 76 gagagagagagagagagaga h 21 77 19 DNA Artificial Sequence Oligonucleotide primer 77actatagggc acgcgtggt 19 78 546 DNA Conyza sp. 78 tagggcgaat tgggccctctagatgcatgc tcgagcggcc gccagtgtga tggatatctg 60 cagaattcgg cttactagagggcacgcgtg gtcgacggcc cgggctggtg atctcatacc 120 agctgaccat cgtatcatcatgtgccaatt agcttgcaaa agttctgaat ttgtaatggt 180 tgatagctgg gaggtctctctctctctctc tctctctctg acacacacac acacacacaa 240 atatgtttta ctaaagctctactttaacat attgcaattt acttttatga ctaaagcatg 300 ttgaatgtag aataagttctttttttaggg cagatgtaga tctgatttac tgataattaa 360 tatcgacctc tttgctgtacaagacctctg cttatttttc tttctatata atgatgcaga 420 gccatttatc ttttttaggcaaaccaaagt tcgtttcaac gctcattgac agtattgtca 480 agaataagga gtttcttttgtgataacgga ctaatatcta gtggtatgtt ctaatgttct 540 atatcc 546 79 445 DNAConyza sp. 79 actagagggc acgcgtggtc gccccgggct ggtgatccat ctgttgttagaggagagaaa 60 cagaagaatg gacttgctct tcctcttgct ggaatgaatt cgacgttggttcatggtgat 120 gactcggcag cggagtttgg tgcgagagag agagacagta agaagatgtgtgtgtatgga 180 gaataaaagg gataatgtgg aagggataat aaggaacgga aaagggtataccaaaaagga 240 aaatgtccaa gggcaatatt ggtattttaa aggcagaagt tactaaaaatagaaaagggt 300 gttttgcttt attaggtagt aaagattgat atcttaaagt gctaatttgactattattta 360 gtttgtcata taaaactttt tcctatattg caacttcatg tttctcattactaaagattt 420 gacaagtgtt atgcaattta ggatc 445 80 454 DNA Conyza sp. 80gatcctccat gggtcaaacc catgacccat cacccaacta acttacccaa ccctatcttc 60cttattttcc acccatccat tcattcttca ccctatcttt ttctttcctt cttcttccaa 120gaacaaaaca cacatacaca ctattgtctc tctctctctc tctctctctc tctaagattc 180ttacaccaaa ttatggtttc aagttagaat tgtgttagaa tcatcatcct tatcatcatc 240ttcattacat atcaaagatt tgggttgtca aaagtgcaag aacatcttct tttgagtaat 300tttcgggttt ggcaatttgt ggaagttttg gtaagtgaat taccagcccg gggccgtcga 360ccacgcgtgc cctttagttc cattcattct tcaccctatc tttttctttc tttcctcttg 420caagaacaaa acacacatac acactaatgt ctct 454 81 254 DNA Conyza sp. 81agcttaggtg tggaatctca catactaatt ttttaatatt gtttgaattt taaataaatc 60acatggcccc catgatattt aaagattaaa aaaagaatat gttagtgttc tacacctaag 120cttagatacg taacaacctt atattcccat ccctctctct ctctctctct gttggatatt 180gtaaacaact attcaaataa aacaaatagg gcaaggtcac cagcccgggc cgtcgaccac 240gcgtgccctg tagt 254 82 247 DNA Conyza sp. 82 actagagggc acgcgtggtcgacggcccgg gctggtgatc tcttaaaaaa tatagacatc 60 cattccataa atattcataacaacaaacaa aatgataatt atttagatat agatataggg 120 tataaaatga gagagagagagagagaaagc gtgtgtgcat acgcgtattg aagagtagca 180 agtcaattga ggtcaggtttagggtttgga agagtcgttt ttcattgata taaccgaaaa 240 acggatc 247 83 339 DNAConyza sp. 83 agctttgaag acttgtttca tcacaccaat tgtcttcacc atcgggctcatcaacttaat 60 tcctacaaga caaaataaca cgtacttcat tcattacaat atatcactaagggggagaat 120 gttagaaatt caaaaatagt gataaattgt aatttaagtt agtggatgttattgttgtta 180 agacatggtg aaatgatttc taaggttgag ggactaggag tgtcaattagcttaattgta 240 gatttagact ataaataccc tcaactcatt agaaatcata agcctttaatccatttttac 300 atacaactta ttcagatcgt ctctctctct ctctctctc 339 84 373 DNAConyza sp. 84 gatccttatt ttgagaacac ctttttctgt aagaaacttg agaactcttaagttatgtat 60 tggatcacat tttttttgtt catcctcatg tgaaacgtta taaaaatatttgtagaaata 120 agtttttttc aaaaccttat atatacaagt ttgatcacat gtgaacgataacgtgaacat 180 attgattcac aagttcacaa aagctatttt gatgggtttt ttaaaaagtttattcttcaa 240 catacttttt tatatcattt cacattaaat taacaaaaaa acatgtgatccaatacataa 300 tttgagagtt ctcgtggttc ttacaaaaaa aatggttttc aaaataaggaaagtctctct 360 ctctctctct ctc 373 85 398 DNA Conyza sp. 85 aattcacatcatcaatggcg gattggaagt gtgtgtgttc ttggtgtgag tgtgtgtttt 60 gagagagaaaatgtgtgtga aaggaaagtg ctttattgga attaatgaga attgtgaagg 120 ttgcaatggttttaaaaagg ctcaaggctt atgatttcta aggtgtgagg ggtatttata 180 ggctaactacacaaatatgc taattatcac atttagccct tcaaccttag tgatcattta 240 cctatgacttaactacaagt aagtccacta atctaaatta caatttatca ctattttgga 300 tttctaacaattgttttata caataaaaag agatgacgac cttttaccga caaatttttt 360 tttaggactctctctcactc tctctctctc tctctctc 398 86 303 DNA Conyza sp. 86 gagagagagagagagagaga cacacacaca gagtgggtgg ggagtaagac tgagagacgg 60 gaaggaattatcggatcgga aggaaggaaa aatgacaagc gcattagtat tcatggctct 120 tgaatgcttcaaatgctcca ccatgcaagt aagtcctcct cttcgatcgt aattgatgga 180 tgtgatttgattaaaaatga tggatggaca acaggtgaag cagaggaaga aaagcagcaa 240 caaatggatctgcgttatct gcaacgagaa gcagtccgtc cggaaggtct attcccaggg 300 atc 303 87397 DNA Conyza sp. misc_feature (336)..(336) Unknown nucleotide 87gagagagaga gagaggagag agacctccct tgatagaatt acctatttca aatacccaat 60tgacggaaac tcccaactaa tccgttcgaa agcacgacga ttaatagggc taaaccctgc 120cggctcagac ttgaacgtgt ttggtctttt atttatagtt cttgtattaa ctggtcacat 180gaatctataa tagattctat aaagataacg aaaaaagagt ttctctaaat tgttgcactg 240gaattgacga agacttaata ccaatattat tctttatttc caagccctca tagaattaat 300atatatatat atctcaaggt tggttgaata aggatntaaa ctttaaacct ataagtcatc 360tggataattt caaaccatta cactaactac tcatcat 397 88 246 DNA Conyza sp.misc_feature (181)..(181) Unknown nucleotide 88 gatccgattg aggacggcggaagcgaatac gacatagcag aagaagatga aaaaaccact 60 aatcatctcc gtgatcgttttcgcctttcc acaatctcta ttgctcaatc tgaaggtctc 120 tctctctctc tctctctctctctctatctc tctctatctc tctctctctc tctctctcta 180 natctctctc tctctctctctctctctctc tttctctctc tctctgtctc tctctctctc 240 tctctc 246 89 184 DNAConyza sp. 89 gagagagaga gagagagaga cttacgaaga agatgaaggt tttgaagaaaatgaaaaaat 60 atttaccttt tggaagaaca atatagatct agatcaggta ggtgaaggttttgaagatga 120 tggaattatg ttgcagctag ggttcatttg tggtgggagg ggcttttggtctattgtctg 180 aatt 184 90 221 DNA Conyza sp. 90 gatccattcc cgggactcaattaggtcaag gccaaatgta aaacacatat atatctcgac 60 atatactccg ggagtgagttaaggaaacat cctctttatc tttcactcta gtttctcttt 120 cctcgagtga gctctcggctggaccccacc ctctagctct cgatctactc ctttctttaa 180 gtttttggtt tacttttctcatctctctct ctctctctct c 221 91 104 DNA Conyza sp. 91 gagagagagagagactgaga gtgttgcggt caatggatcg aatcctgatc cggcggatgc 60 aaaggatactccggtcatga ggtcttgaat cgtaagtgtt ggat 104 92 286 DNA Conyza sp. 92gatccaactt gagatgatgt atccatatgc ggtttttttg gacttgatcg aattgagaga 60attagagatc tgaaagttaa aatttgggaa gtcattccaa gaggacccca tctttagaga 120gatcaatgtg atgcttacat atgacaacaa taatcagggc tgggcagtgg tatggcatgg 180cctgatagaa gatgactcaa agagcttgac taattgggtg agggtggatg actctcttaa 240agagcttcac tattctttct actccttctc tctctctctc tctctc 286 93 153 DNA Conyzasp. 93 gatcctccat gggtcaaacc catgacccat cacccaaccc tatcttcctt attttccacc60 catccattca ttcttcaccc tatctttttc tttctttctt cttgcaagaa caaaacacac 120atacacacta atgtctctct ctctctctct ctc 153 94 153 DNA Conyza sp. 94gagagagaga gagagagaga cattagtgtg tatgtgtgtt ttgttcttgc aagaagaaag 60aaagaaaaag atagggtgaa gaatgaatgg atgggtggaa aataaggaag atagggttgg 120gtgatgggtc atgggtttga cccatggagg atc 153 95 509 DNA Conyza sp.misc_feature (481)..(481) Unknown nucleotide 95 gagagagaga gagagagagacgatctgatt tgttgtatgt gtaaaaatgg ataaaaggct 60 tattggttgt tgctatgatttctaatgtat tgagggtatt tatactctaa tattacaaat 120 atccttattg tcatatctaacccctcaaca ttagaaatca tttcaccatg tctaaacaac 180 aattaagtcc actaacttaaattacaattt atcactattt ttggatttct aacaatcact 240 gtttgtcact ccatcgaatttctcttcctc aacactcttc aaatgatttc cttttaagag 300 taaaattcaa cccggtggctggagaacgaa tagcattgcc acggttggcc ggtatatttc 360 tccttcgatc cccgtaaagaaggttgttgg ggttgactgg ttgttcctga tcaccaattc 420 ttcttgcctg aactggttgatttacccgaa gaattactgt tgaaccaggt atagaagtct 480 ngtccttatt atcgtccttttctgaacta 509 96 343 DNA Conyza sp. misc_feature (207)..(207) Unknownnucleotide 96 gagagagaga gagagagaga cgatacctga gattttgggc ggcaagaagtgaggcgaaat 60 tcctttgaag attgtttgat ggtgaaagtg aagtgggatg caggttgaaaacaaaggagt 120 aaaaccctat tatttaccga tgaagaggtt aacagctgaa tggttttagacctaacttgt 180 taacggttga agttaagaga cggtacngat aacttaaaag aataccaaaattataaattt 240 aactttttta atatttaagt taaaataaat ttaatttttt cgataccttttttccccatc 300 atccctataa ttcaaaatca taaaaggatg tgtgtaatgg atc 343 97111 DNA Conyza sp. 97 gagagagaga gagagagaga ctgagagtgt tgcggtcaatggatcgaatc ctgatccggc 60 ggatgcaaag gatactccgg tcatgaggtc ttgaatcgtaagtgttggat c 111 98 60 DNA Conyza sp. 98 cgacggcccc gggctggtgatccacatcaa cggtcacacg tctctctctc tctctctctc 60 99 158 DNA Conyza sp. 99atattagtct aagtgctgga atctaaattt gcctcccaca ccccctttat ctcagatttt 60atttcctcca accctccatt tcttatctac ctttctctct ctaattctct tccatgaaca 120cacacacaaa catacctgtc tctctctctc tctctctc 158 100 558 DNA Conyza sp. 100gatccctatc cgtttcaaat atagtaacaa aatgttaact atttcacaga gtatatattt 60tcctagcaac gtgatttagt acactttggg tgattttcta catataccta cctttttggc 120tatttttcta atttacctgt gtgctgtttt agatacagaa cacatagcat gcatttgagt 180atcgcctcat ttataagtaa ctcggtcaaa gttgtcatct ctcgagagtt cccataagtt 240aattctcttt ttggttcttt taggtgaaca aaggaactgc tagtgcaagt gagattttag 300ctggtgcatt gaaggataac aagcgtgcag tgcttcttgg agaacccact tacggcaaag 360ggtaatcaat tttgcataat gcttcttaat agcataacat ccttgatcag atgtctcagg 420aataaatgat ccttattcac agaaaaatcc aatcggtttt tgaattgtct gatggctctg 480gcttggctgt tactgttgct cgatatgaaa cccctgatca cattgacatc aataaggttc 540tctctctctc tctctctc 558 101 166 DNA Conyza sp. 101 gatcctccat gggtcaaacccatgacccat cacccaacta acttacccaa ccctatcttc 60 cttattttca acccatccattcattcttca ccctatcttt ttctttcctt cttcttccaa 120 gaacaaaaca cacatacacactattgtctc tctctctctc tctctc 166 102 390 DNA Conyza sp. 102 gagagagagagagagaagga gagagagaga gagagagaga aggagagaga gagagagaga 60 gagagagagaagagagagag agagagagag atagagagag agtgagagag agagagagac 120 gatctaaatgtaaaaatgga tgaaaggctt attgaggtgt tgttatgatt tctaatgtat 180 agagggtatatatactctaa tattacaaat atccttattg tcatatctaa cccctcaacg 240 ttagaaatcatttcaccatg tctaaacaac aattaagtcc actaacttaa attacaagtt 300 atcactatttttggatttct aacagaaatg ttgtagactt ttatttggtt tagttgcaac 360 tatttgatggaatgtaaatg gagagggatc 390 103 413 DNA Conyza sp. 103 tctctctctctctctctctc aagccgaatt ccagcacact ggcggccgtt actagtggat 60 ccgagctcggtaccaagctt ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt 120 tatccgctcacaattccaca caacatacga gccggaagca taaagtgtaa agcctggggt 180 gcctaatgagtgagctaact cacattaatt gcgttgcgct cactgcccgc tttccagtcg 240 ggaaacctgtcgtgccagct gcattaatga atcggccaac gcgcggggag aggcggtttg 300 cgtattgggcgctcttccgc ttcctcgctc actgactcgc tgcgctcggt cgttcggctg 360 cggcgagcggtatcagctca ctcaaaggcg gtaatacggt tatccacaga atc 413 104 405 DNA Conyzasp. 104 gagagagaga gagagggaga gagagagagc agagagacaa agagacatacagcaaaccat 60 ataaactcct tggttgcaag aggtcttgta atttcatgcc ttttcagtgattcttcaaca 120 gtgccttgaa ccttcacata gaacaaaacc ttttaatatt gatttagattaaaatgagct 180 aagatagtat ttgtcccact gaaagaaaag cataagttac atttaagagaaccaaaattt 240 atgtattagc tacaaagcta acagttgatc aatacattct ataagtgagtcggttctggg 300 tgtttggtgg ttaattttag gtaccgtgaa tccgtgatcc actgctgcaacacttggagc 360 aacatcgttt ggaaaaacat atgaggacta tttgcttgtt tctcc 405 105385 DNA Conyza sp. 105 gagagagaga gagagagaga cattagtgtg tatgtgtgtattgttcttgc aagaagaaag 60 aaagaaaaag atagggtgaa gaatgaatgg atgggtggaaaataaggaag atagggttgg 120 gtaagtaagt tgggtgatgg gtttgaccca tggaggatcaccagcccggg gccgtcgacc 180 acgcgtgccc tttagtaagc cgaatgccag cacactggcggccgttacta gtggatccga 240 gctcggtacc aagcttggcg taatcatggt catagctgtttcctgtgtga aattgttatc 300 cgctcacaat tccacacaac atacgagccg gaagcataaagtgtaaagcc tggggtgcct 360 aatgagtgag ctaactcaca tgaat 385 106 347 DNAConyza sp. 106 gagagagaga gagagagaga gagagagacg atctgaataa gttgtatgtaaaagtggata 60 aaaggcttat gatttctaag gagttgaggg tatttatagt ctaaatctacaattaagcta 120 attgacactc ctagtccctc aaccttagaa atcatttcac catgtcttaacaacaacaac 180 gtccactaac ttaaatttca atttatcact atttttgaat ttctaaaattctctccctta 240 gtgatatatt gtaatgaatg aagtacgtgt tattttgtct tgtaggaattaagttgatga 300 gcccgatggt gaagacaatt ggtgtgatga aacaagtctt caaagct 347107 152 DNA Conyza sp. 107 gagagagaga gagagagaga cctggaagaa gccccattctttagaagctg cgtgtagctt 60 attcagctca tcagaagaaa tgtcactgga agtgtttgcaaagaggtttt gaaggtcgat 120 gaccggcacg gatgatgtgg tagtagtcaa cg 152 108 88DNA Conyza sp. 108 gagagagaga gagagagaga cgatctgaat aagttgtatgtaaaaatgga tcaccagccc 60 gggccgtcga ccacgcgtgc cctttagt 88 109 314 DNAConyza sp. 109 actaaagggc acgcgtggtc gacggcccgg gctggtgatc aaatgaaagttgacatactt 60 tgtgaaattg tgtataaatt attcataagc aaacaaggaa gctctttattttcatcgatc 120 tctttttggg tacgtctaac cttttttttg ttatgatcta aggccggttcttataataga 180 aggagtcctt aggagtcctg actgccacgt caacaatagg actctccttaggactctccc 240 tgcctataat gacaagcttt tttagatctt ggtcccacct ctttactttctccctctctc 300 tctctctctc tctc 314 110 438 DNA Conyza sp. 110 gagagagagagagagagaga gcgggggagt tagggtaaaa taaaaaacta ttaacctaaa 60 ataagtaagacatcacaaaa aagtgacatg tggcatgaga atatttaaaa ttaaattata 120 atttcaagggtaatatggac attatgtaaa attaatatct ggcttctata attgatgtaa 180 cccatcgtgtattagaccct aatttgttag aaatccaaaa atagtgataa attgtaattt 240 aagttagtggatgttattgt tgttaagaca tggtgaaatg atttctaatg ttgaggggtt 300 agatatgacaataaggatat ttgtaatatt agagtataaa taccctcaat acattagaaa 360 tcataacaacaattaagcct tttatccatt ttacaaatac aacatatata gatcgcctct 420 ctctctctctctctctct 438 111 202 DNA Conyza sp. 111 gagagagaga gagagagaga gggggagttagggtaaaata aaaaactatt aacctaaaat 60 aagtaagaca tcataaaaaa gtgacatgtggcatgagaat atttaaaatt aaattataat 120 gtcaagggta atatggacat tatgtaaaattaatatctgg cttctataat tgatgtaacc 180 catcgtgtat aagaccctaa tt 202 112 91DNA Conyza sp. 112 agagagagga gagagagagg gccgatctga ataagttgtatgtaaaaaat ggatcaccag 60 cccgggccgt cgaccacgcg tgccctctag t 91 113 19DNA Artificial Sequence Oligonucleotide primer 113 ccatcgtatc atcatgtgc19 114 18 DNA Artificial Sequence Oligonucleotide primer 114 tagcttgcaaaagttctg 18 115 21 DNA Artificial Sequence Oligonucleotide primer 115tgcaatatgt taaagtagag c 21 116 18 DNA Artificial SequenceOligonucleotide primer 116 taccaatatt gcccttgg 18 117 19 DNA ArtificialSequence Oligonucleotide primer 117 gtataccctt ttccgttcc 19 118 22 DNAArtificial Sequence Oligonucleotide primer 118 ttcatggtga tgactcggca gc22 119 18 DNA Artificial Sequence Oligonucleotide primer 119 tacccaaccctatcttcc 18 120 18 DNA Artificial Sequence Oligonucleotide primer 120tccattcatt cttcaccc 18 121 21 DNA Artificial Sequence Oligonucleotideprimer 121 ccataatttg gtgtaagaat c 21 122 18 DNA Artificial SequenceOligonucleotide primer 122 atgttagtgt tctacacc 18 123 18 DNA ArtificialSequence Oligonucleotide primer 123 cttagatacg taacaacc 18 124 18 DNAArtificial Sequence Oligonucleotide primer 124 aacgactctt ccaaaccc 18125 18 DNA Artificial Sequence Oligonucleotide primer 125 tgacctcaattgacttgc 18 126 18 DNA Artificial Sequence Oligonucleotide primer 126atatagacat ccattcca 18 127 259 DNA Conyza sp. 127 cacatcttta gcatcggccaccattgaaaa agtggctgaa tcgtggtata agaatgttgt 60 attgcaggtt gatgttgagagggatttgga tgatttgaat ggtggtgcca gaattctact 120 gctgagtcat ctttgcatgatttccatgca aaaggtggtg ctactcatgt ttcccctatg 180 cttgatcctc ctaagtttcctcctggtact acttatttta agccagctac agacacatgc 240 caatgacatt cttgatgtt 259128 287 DNA Conyza sp. 128 cacatcttta gcatcggcca ccattgaaaa agtggctgaatcatgggata aaaatgtcgc 60 tacaagtgtt gatgatggta gggacttgaa tgattctaatggtgatggcc ttcactcgac 120 tgttgaacca acattgcgtg gtttgcatgc atatgttggtgattctaatg tacctccaaa 180 ccaaagttcc ctcctgatgc ttcttatttt caaccggctgcatgtcatgc aaatgacatt 240 caccctgcta cagatgaggc ccctttgcat gatgtttctccgaatga 287 129 348 DNA Conyza sp. 129 atggtaggga tttgaatgat tcgactggggatggcttaca ctcgactgct gaaccaacat 60 tgcatggttt gcatgcaaat gttgatgattgtactgtgcc tcctatgccg gaaccgccaa 120 agttccctcc tgatgctact tactttcagccggctgcatg tcatgtaaat gacattcatc 180 ctgcttcaca tgaggcccct tatgcatgatgttactccta atgatcttag tggataccct 240 gacagtccta aggtccagca gccgcgtacttatgcttcta tctttcagga tgcggctaac 300 atcaacaaga aaggtaaatt gagattcatccctccaaaaa aaaaaaaa 348

What is claimed is:
 1. A method for identifying polymorphic markers ofherbicide resistance in a plant comprising: (a) isolating genomic DNAfrom an herbicide susceptible plant and an herbicide resistant plant ofthe same species; (b) performing genetic analysis on said genomic DNA ofsaid an herbicide susceptible plant and said herbicide resistant plant;and (c) identifying differences between the genomic DNA of saidherbicide susceptible plant and said herbicide resistant plant, (d)identifying said differences that correlate with herbicide resistance orherbicide susceptibility by screening samples of herbicide resistant andherbicide susceptible plants; thereby identifying polymorphic markers ofherbicide resistance in said plant.
 2. The method of claim 1 whereinsaid polymorphic markers comprise polynucleotide microsatellite markerswhere herbicide resistant plants have a distinct haplotype pattern incomparison to herbicide susceptible species.
 3. The method of claim 1wherein said plant is Conyza canadensis.
 4. The method of claim 1wherein said plant is Lolium rigidum.
 5. The method of claim 1 whereinsaid plant is a goosegrass species.
 6. The method of claim 1 whereinsaid herbicide comprises glyphosate.
 7. The method of claim 1 whereinsaid herbicide comprises paraquot.
 8. The method of claim 1 wherein saidherbicide comprises sulfonyl urea moities.
 9. A method for generatingherbicide susceptible weeds from herbicide resistant weeds comprising:(a) mutagenizing said resistant weeds, thereby creating mutant parentalweeds; (b) testing progeny of said mutant parental weeds forsusceptibility to said herbicide; and (c) selecting said mutant parentalweeds producing herbicide susceptible progeny.
 10. The method of claim 9wherein the step of testing comprises analyzing said progeny forresistance to an herbicide selected from the group consisting ofaminoglycosides, 5-enolpyruvylshikimate-3-phosphate synthase inhibitors,triazine-based herbicides, beta-lactams, macrolides, lincosamides,sulfonamides, atrazine, alachlor, isoniazids, and metribuzin.
 11. Themethod of claim 9 wherein said mutagenizing is accomplished byintroducing into said herbicide resistant weed a dominant negativeallele of a mismatch repair gene.
 12. The method of claim 11 whereinsaid dominant negative allele of a mismatch gene is a dominant negativeallele of a gene encoding a mismatch repair protein selected from thegroup consisting of PMS2, PMS1, MLH1, MSH2, MSH3, MSH6, MSH7, MSH6-1,PMSR2, PMSR3, and PMSL9.
 13. The method of claim 12 wherein saiddominant negative allele is a PMS2 truncation mutant.
 14. The method ofclaim 13 wherein said truncation mutant encodes PMS2-134.
 15. The methodof claim 9 wherein said mutagenizing is accomplished by introducing intosaid herbicide resistant weed a chemical inhibitor of mismatch repairselected from the group consisting of an anthracene, an ATPaseinhibitor, a nuclease inhibitor, a polymerase inhibitor and an antisenseoligonucleotide that specifically hybridizes to a nucleotide encoding amismatch repair protein dominant negative allele of a mismatch repairgene.
 16. The method of claim 15 wherein said chemical inhibitor is ananthracene having the formula:

wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino, alkyl,substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substitutedalkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl, aryloxy,substituted aryloxy, heteroaryl, substituted heteroaryl, aralkyloxy,arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl, alkylsulfonyl,alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, an alcohol, anamino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehyde group, anester, an ether, a crown ether, a ketone, an organosulfur compound, anorganometallic group, a carboxylic acid, an organosilicon or acarbohydrate that optionally contains one or more alkylated hydroxylgroups; wherein said heteroalkyl, heteroaryl, and substituted heteroarylcontain at least one heteroatom that is oxygen, sulfur, a metal atom,phosphorus, silicon or nitrogen; and wherein said substituents of saidsubstituted alkyl, substituted alkenyl, substituted alkynyl, substitutedaryl, and substituted heteroaryl are halogen, CN, NO₂, lower alkyl,aryl, heteroaryl, aralkyl, aralkoxy, guanidino, alkoxycarbonyl, alkoxy,hydroxy, carboxy and amino; and wherein said amino groups are optionallysubstituted with an acyl group, or 1 to 3 aryl or lower alkyl groups.17. The method of claim 16 wherein R₅ and R₆ are hydrogen.
 18. Themethod of claim 16 wherein R₁-R₁₀ are independently hydrogen, hydroxyl,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, tolyl,hydroxymethyl, hydroxypropyl, or hydroxybutyl.
 19. The method of claim16 wherein said chemical inhibitor of mismatch repair is selected fromthe group consisting of 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.
 20. The method of claim 9 wherein saidmutagenizing is accomplished using T-DNA insertional mutagenesis.
 21. Amethod for generating herbicide resistant weeds from herbicidesusceptible weeds comprising: (a) mutagenizing said susceptible weeds,thereby creating mutant parental weeds; (b) testing progeny of saidmutant parental weeds for resistance to said herbicide; and (c)selecting said mutant parental weeds producing herbicide resistantprogeny.
 22. The method of claim 21 wherein the step of testingcomprises analyzing said progeny for susceptibility to an herbicideselected from the group consisting of aminoglycosides,5-enolpyruvylshikimate-3-phosphate synthase inhibitors, triazine-basedherbicides, beta-lactams, macrolides, lincosamides, sulfonamides,atrazine, alachlor, isoniazids, and metribuzin.
 23. The method of claim21 wherein said mutagenizing is accomplished by introducing into saidherbicide resistant weed a dominant negative allele of a mismatch repairgene.
 24. The method of claim 23 wherein said dominant negative alleleof a mismatch gene is a dominant negative allele of a gene encoding amismatch repair gene selected from the group consisting of PMS2, PMS1,MLH1, MSH2, MSH3, MSH6-1, MSH7, MSH6, PMSR2, PMSR3, and PMSL9.
 25. Themethod of claim 24 wherein said dominant negative allele is a PMS2truncation mutant.
 26. The method of claim 25 wherein said truncationmutant encodes PMS2-134.
 27. The method of claim 21 wherein saidmutagenizing is accomplished by introducing into said herbicideresistant weed a chemical inhibitor of mismatch repair selected from thegroup consisting of an anthracene, an ATPase inhibitor, a nucleaseinhibitor, a polymerase inhibitor and an antisense oligonucleotide thatspecifically hybridizes to a nucleotide encoding a mismatch repairprotein dominant negative allele of a mismatch repair gene.
 28. Themethod of claim 27 wherein said chemical inhibitor is an anthracenehaving the formula:

wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino, alkyl,substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substitutedalkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl, aryloxy,substituted aryloxy, heteroaryl, substituted heteroaryl, aralkyloxy,arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl, alkylsulfonyl,alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, an alcohol, anamino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehyde group, anester, an ether, a crown ether, a ketone, an organosulfur compound, anorganometallic group, a carboxylic acid, an organosilicon or acarbohydrate that optionally contains one or more alkylated hydroxylgroups; wherein said heteroalkyl, heteroaryl, and substituted heteroarylcontain at least one heteroatom that is oxygen, sulfur, a metal atom,phosphorus, silicon or nitrogen; and wherein said substituents of saidsubstituted alkyl, substituted alkenyl, substituted alkynyl, substitutedaryl, and substituted heteroaryl are halogen, CN, NO₂, lower alkyl,aryl, heteroaryl, aralkyl, aralkoxy, guanidino, alkoxycarbonyl, alkoxy,hydroxy, carboxy and amino; and wherein said amino groups are optionallysubstituted with an acyl group, or 1 to 3 aryl or lower alkyl groups.29. The method of claim 28 wherein R₅ and R₆ are hydrogen.
 30. Themethod of claim 28 wherein R₁-R₁₀ are independently hydrogen, hydroxyl,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, tolyl,hydroxymethyl, hydroxypropyl, or hydroxybutyl.
 31. The method of claim28 wherein said chemical inhibitor of mismatch repair is selected fromthe group consisting of 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.
 32. The method of claim 21 wherein saidmutagenizing is accomplished using T-DNA insertional mutagenesis.
 33. Amethod for identifying a mutant gene conferring herbicide resistancecomprising (a) comparing the genome of a naturally occurring herbicideresistant plant to the genome of an herbicide susceptible plant; (b)determining genetic differences between said herbicide resistant plantto the herbicide susceptible plant; and (c) sequencing a region of DNAcomprising said genetic difference.
 34. The method of claim 33 whereinsaid genome of said herbicide resistant plant and said genome of saidherbicide susceptible plant are compared by a technique selected fromthe group consisting of microarray analysis, genotyping of repetitivesequences using microsatellite markers to identify linked genomicsegments that are associated with a particular trait, single nucleotidepolymorphic (SNP) analysis, restriction fragment length polymorphism(RFLP) analysis, amplified fragment length polymorphism (AFLP) analysis,simple sequence length polymorphism analysis (SSLPs), randomly amplifiedpolymorphic DNAs (RAPDs), DNA amplification fingerprinting (DAF),sequence characterized amplified regions (SCARs), arbitrary primedpolymerase chain reaction (AP-PCR), and single nucleotide polymorphisms(SNPs).
 35. A method for identifying a mutant gene conferring herbicideresistance comprising introducing into an herbicide susceptible weedgene fragments from an herbicide resistant weed, thereby creating atransfected herbicide susceptible strain; (a) screening progeny of saidtransfected herbicide susceptible strain for herbicide resistance; and(b) sequencing said gene fragment to identify an herbicide resistancegene.
 36. The method of claim 35 wherein said genome of said herbicideresistant plant and said genome of said herbicide susceptible plant arecompared by a technique selected from the group consisting of microarrayanalysis, genotyping of repetitive sequences using microsatellitemarkers to identify linked genomic segments that are associated with aparticular trait, single nucleotide polymorphic (SNP) analysis,restriction fragment length polymorphism (RFLP) analysis, amplifiedfragment length polymorphism (AFLP) analysis, simple sequence lengthpolymorphism analysis (SSLPs), randomly amplified polymorphic DNAs(RAPDs), DNA amplification fingerprinting (DAF), sequence characterizedamplified regions (SCARs), arbitrary primed polymerase chain reaction(AP-PCR), and single nucleotide polymorphisms (SNPs).
 37. A method foridentifying a mutant gene conferring herbicide susceptibility comprising(a) introducing into an herbicide resistant weed gene fragments from anherbicide susceptible weed, thereby creating a transfected herbicideresistant strain; (b) screening progeny of said transfected herbicideresistant strain for herbicide susceptibility; and (c) sequencing saidgene fragment to identify an herbicide susceptibility gene.
 38. Themethod of claim 37 wherein said genome of said herbicide resistant plantand said genome of said herbicide susceptible plant are compared by atechnique selected from the group consisting of microarray analysis,genotyping of repetitive sequences using microsatellite markers toidentify linked genomic segments that are associated with a particulartrait, single nucleotide polymorphic (SNP) analysis, restrictionfragment length polymorphism (RFLP) analysis, amplified fragment lengthpolymorphism (AFLP) analysis, simple sequence length polymorphismanalysis (SSLPs), randomly amplified polymorphic DNAs (RAPDs), DNAamplification fingerprinting (DAF), sequence characterized amplifiedregions (SCARs), arbitrary primed polymerase chain reaction (AP-PCR),and single nucleotide polymorphisms (SNPs).
 39. A method for identifyinga mutant gene conferring herbicide susceptibility comprising (a)crossing an herbicide resistant weed with an herbicide susceptible weed,thereby creating a crossed strain; (b) screening progeny for herbicidesusceptibility; and (c) performing genetic analysis on said crossedstrain producing herbicide susceptible progeny to identify an herbicidesusceptibility gene.
 40. The method of claim 39 wherein said genome ofsaid herbicide resistant plant and said genome of said herbicidesusceptible plant are compared by a technique selected from the groupconsisting of microarray analysis, genotyping of repetitive sequencesusing microsatellite markers to identify linked genomic segments thatare associated with a particular trait, single nucleotide polymorphic(SNP) analysis, restriction fragment length polymorphism (RFLP)analysis, amplified fragment length polymorphism (AFLP) analysis, simplesequence length polymorphism analysis (SSLPs), randomly amplifiedpolymorphic DNAs (RAPDs), DNA amplification fingerprinting (DAF),sequence characterized amplified regions (SCARs), arbitrary primedpolymerase chain reaction (AP-PCR), and single nucleotide polymorphisms(SNPs).
 41. The method of claim 39 further comprising the step ofperforming at least one backcross of said progeny with said crossedstrain.
 42. A method for identifying a mutant gene conferring herbicideresistance comprising: (a) crossing an herbicide resistant weed with anherbicide susceptible weed, thereby creating a crossed strain; (b)screening progeny for herbicide resistance; and (c) performing geneticanalysis on said crossed strain producing herbicide resistant progeny toidentify an herbicide resistance gene.
 43. The method of claim 42wherein said genome of said herbicide resistant plant and said genome ofsaid herbicide susceptible plant are compared by a technique selectedfrom the group consisting of microarray analysis, genotyping ofrepetitive sequences using microsatellite markers to identify linkedgenomic segments that are associated with a particular trait, singlenucleotide polymorphic (SNP) analysis, restriction fragment lengthpolymorphism (RFLP) analysis, amplified fragment length polymorphism(AFLP) analysis, simple sequence length polymorphism analysis (SSLPs),randomly amplified polymorphic DNAs (RAPDs), DNA amplificationfingerprinting (DAF), sequence characterized amplified regions (SCARs),arbitrary primed polymerase chain reaction (AP-PCR), and singlenucleotide polymorphisms (SNPs).
 44. The method of claim 42 furthercomprising the step of performing at least one backcross of said progenywith said crossed strain.
 45. A method for identifying a mutant geneconferring herbicide resistance comprising (a) mutagenizing an herbicidesusceptible weed, thereby creating mutant parental weeds; (b) testingprogeny of said mutant parental weeds for resistance to said herbicide;and (c) comparing the genome of a naturally occurring herbicideresistant plant to the genome of an herbicide susceptible plant; (d)determining genetic differences between said herbicide resistant plantto the herbicide susceptible plant; and (e) sequencing a region of DNAcomprising said genetic difference.
 46. The method of claim 45 whereinsaid mutagenizing is accomplished by introducing into said herbicideresistant weed a dominant negative allele of a mismatch repair gene. 47.The method of claim 45 wherein said dominant negative allele of amismatch gene is a dominant negative allele of a gene encoding amismatch repair protein selected from the group consisting of PMS2,PMS1, MLH1, MSH2, MSH3, MSH6-1, MSH7, MSH6, PMSR2, PMSR3, and PMSL9. 48.The method of claim 47 wherein said dominant negative allele is a PMS2truncation mutant.
 49. The method of claim 48 wherein said truncationmutant encodes PMS2-134.
 50. The method of claim 45 wherein saidmutagenizing is accomplished by introducing into said herbicideresistant weed a chemical inhibitor of mismatch repair selected from thegroup consisting of an anthracene, an ATPase inhibitor, a nucleaseinhibitor, a polymerase inhibitor and an antisense oligonucleotide thatspecifically hybridizes to a nucleotide encoding a mismatch repairprotein dominant negative allele of a mismatch repair gene.
 51. Themethod of claim 50 wherein said chemical inhibitor is an anthracenehaving the formula:

wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino, alkyl,substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substitutedalkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl, aryloxy,substituted aryloxy, heteroaryl, substituted heteroaryl, aralkyloxy,arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl, alkylsulfonyl,alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, an alcohol, anamino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehyde group, anester, an ether, a crown ether, a ketone, an organosulfur compound, anorganometallic group, a carboxylic acid, an organosilicon or acarbohydrate that optionally contains one or more alkylated hydroxylgroups; wherein said heteroalkyl, heteroaryl, and substituted heteroarylcontain at least one heteroatom that is oxygen, sulfur, a metal atom,phosphorus, silicon or nitrogen; and wherein said substituents of saidsubstituted alkyl, substituted alkenyl, substituted alkynyl, substitutedaryl, and substituted heteroaryl are halogen, CN, NO₂, lower alkyl,aryl, heteroaryl, aralkyl, aralkoxy, guanidino, alkoxycarbonyl, alkoxy,hydroxy, carboxy and amino; and wherein said amino groups are optionallysubstituted with an acyl group, or 1 to 3 aryl or lower alkyl groups.52. The method of claim 51 wherein R₅ and R₆ are hydrogen.
 53. Themethod of claim 51 wherein R₁-R₁₀ are independently hydrogen, hydroxyl,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, tolyl,hydroxymethyl, hydroxypropyl, or hydroxybutyl.
 54. The method of claim51 wherein said chemical inhibitor of mismatch repair is selected fromthe group consisting of 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.
 55. A method for identifying a mutant geneconferring herbicide resistance comprising (a) mutagenizing an herbicideresistant weed, thereby creating mutant parental weeds; (b) testingprogeny of said mutant parental weeds for susceptibility to saidherbicide; and (c) comparing the genome of a naturally occurringherbicide resistant plant to the genome of an herbicide susceptibleplant; (d) determining genetic differences between said herbicideresistant plant to the herbicide susceptible plant; and (e) sequencing aregion of DNA comprising said genetic difference.
 56. The method ofclaim 55 wherein said mutagenizing is accomplished by introducing intosaid herbicide resistant weed a dominant negative allele of a mismatchrepair gene.
 57. The method of claim 55 wherein said dominant negativeallele of a mismatch gene is a dominant negative allele of a geneencoding a mismatch repair protein selected from the group consisting ofPMS2, PMS1, MLH1, MSH2, MSH3, MSH6-1, MSH7, MSH6, PMSR2, PMSR3, andPMSL9.
 58. The method of claim 57 wherein said dominant negative alleleis a PMS2 truncation mutant.
 59. The method of claim 58 wherein saidtruncation mutant encodes PMS2-134.
 60. The method of claim 55 whereinsaid mutagenizing is accomplished by introducing into said herbicideresistant weed a chemical inhibitor of mismatch repair selected from thegroup consisting of an anthracene, an ATPase inhibitor, a nucleaseinhibitor, a polymerase inhibitor and an antisense oligonucleotide thatspecifically hybridizes to a nucleotide encoding a mismatch repairprotein dominant negative allele of a mismatch repair gene.
 61. Themethod of claim 60 wherein said chemical inhibitor is an anthracenehaving the formula:

wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino, alkyl,substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substitutedalkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl, aryloxy,substituted aryloxy, heteroaryl, substituted heteroaryl, aralkyloxy,arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl, alkylsulfonyl,alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, an alcohol, anamino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehyde group, anester, an ether, a crown ether, a ketone, an organosulfur compound, anorganometallic group, a carboxylic acid, an organosilicon or acarbohydrate that optionally contains one or more alkylated hydroxylgroups; wherein said heteroalkyl, heteroaryl, and substituted heteroarylcontain at least one heteroatom that is oxygen, sulfur, a metal atom,phosphorus, silicon or nitrogen; and wherein said substituents of saidsubstituted alkyl, substituted alkenyl, substituted alkynyl, substitutedaryl, and substituted heteroaryl are halogen, CN, NO₂, lower alkyl,aryl, heteroaryl, aralkyl, aralkoxy, guanidino, alkoxycarbonyl, alkoxy,hydroxy, carboxy and amino; and wherein said amino groups are optionallysubstituted with an acyl group, or 1 to 3 aryl or lower alkyl groups.62. The method of claim 61 wherein R₅ and R₆ are hydrogen.
 63. Themethod of claim 61 wherein R₁-R₁₀ are independently hydrogen, hydroxyl,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, tolyl,hydroxymethyl, hydroxypropyl, or hydroxybutyl.
 64. The method of claim61 wherein said chemical inhibitor of mismatch repair is selected fromthe group consisting of 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.
 65. A polymorphic DNA marker for identifyingherbicide resistant and herbicide susceptible weeds comprising apolynucleotide sequence encoding a polypeptide comprising SEQ ID NO: 17.66. The polymorphic DNA marker of claim 65 wherein said polynucleotidecomprises the sequence of SEQ ID NO:
 16. 67. A kit for theidentification of herbicide resistant and herbicide susceptible weedscomprising, in one or more containers, an oligonucleotide primercomprising the sequence of SEQ ID NO: 18, and a second oligonucleotideprimer comprising the sequence of SEQ ID NO:
 19. 68. The kit of claim 67further comprising at least one other component selected from the groupconsisting of a DNA polymerase, deoxynucleotide triphosphates, genomicDNA from an herbicide susceptible plant, genomic DNA from an herbicideresistant plant, and DNA polymerase buffer.
 69. A method for generatinggenetically stable glyphosate susceptible weeds derived from glyphosateresistant parental weeds comprising: (a) contacting said glyphosatesusceptible weed with an inhibitor of mismatch repair, thereby forming ahypermutable parental weed; (b) testing progeny of said hypermutableparental weed that are glyphosate susceptible; (c) selectinghypermutable parental strains producing glyphosate susceptible progeny;(d) removing said inhibitor of mismatch repair from said hypermutableparental weed, thereby making said hypermutable parental weedgenetically stable; and (e) obtaining progeny from genetically stableparental weed.
 70. The method of claim 69 wherein said inhibitor ofmismatch repair is a dominant negative allele of a mismatch repair gene.71. The method of claim 70 wherein said dominant negative allele of saidmismatch repair gene is PMS2-134.
 72. The method of claim 69 whereinsaid inhibitor of mismatch repair is a chemical inhibitor of mismatchrepair.
 73. The method of claim 72 wherein said chemical inhibitor ofmismatch repair is selected from the group consisting of an anthracene,an ATPase inhibitor, a nuclease inhibitor, a polymerase inhibitor and anantisense oligonucleotide that specifically hybridizes to a nucleotideencoding a mismatch repair protein.
 74. The method of claim 73 whereinsaid chemical inhibitor is an anthracene having the formula:

wherein R₁-R₁₀ are independently hydrogen, hydroxyl, amino, alkyl,substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substitutedalkynyl, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,O-alkynyl, S-alkynyl, N-alkynyl, aryl, substituted aryl, aryloxy,substituted aryloxy, heteroaryl, substituted heteroaryl, aralkyloxy,arylalkyl, alkylaryl, alkylaryloxy, arylsulfonyl, alkylsulfonyl,alkoxycarbonyl, aryloxycarbonyl, guanidino, carboxy, an alcohol, anamino acid, sulfonate, alkyl sulfonate, CN, NO₂, an aldehyde group, anester, an ether, a crown ether, a ketone, an organosulfur compound, anorganometallic group, a carboxylic acid, an organosilicon or acarbohydrate that optionally contains one or more alkylated hydroxylgroups; wherein said heteroalkyl, heteroaryl, and substituted heteroarylcontain at least one heteroatom that is oxygen, sulfur, a metal atom,phosphorus, silicon or nitrogen; and wherein said substituents of saidsubstituted alkyl, substituted alkenyl, substituted alkynyl, substitutedaryl, and substituted heteroaryl are halogen, CN, NO₂, lower alkyl,aryl, heteroaryl, aralkyl, aralkoxy, guanidino, alkoxycarbonyl, alkoxy,hydroxy, carboxy and amino; and wherein said amino groups are optionallysubstituted with an acyl group, or 1 to 3 aryl or lower alkyl groups.75. The method of claim 74 wherein R₅ and R₆ are hydrogen.
 76. Themethod of claim 74 wherein R₁-R₁₀ are independently hydrogen, hydroxyl,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, tolyl,hydroxymethyl, hydroxypropyl, or hydroxybutyl.
 77. The method of claim74 wherein said chemical inhibitor of mismatch repair is selected fromthe group consisting of 1,2-dimethylanthracene, 9,10-dimethylanthracene,7,8-dimethylanthracene, 9,10-diphenylanthracene,9,10-dihydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene,dimethylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-1,2-diol,9-hydroxymethyl-10-methylanthracene-3,4-diol, and9,10-di-m-tolylanthracene.
 78. An oligonucleotide primer that annealsunder PCR conditions to a polymorphic marker in genomic DNA or cDNA of aplant, wherein the nucleotide sequence of said polymorphic marker isselected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 60, SEQID NO: 61, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO:77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ IDNO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91,SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO:96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ IDNO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105,SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ IDNO: 110, and SEQ ID NO: 111, and wherein said oligonucleotide primer isat least 15 nucleotides in length, and comprising at least 85% identityto a region of said polymorphic marker.
 79. The oligonucleotide primerof claim 78 wherein said primer comprises a nucleotide sequence selectedfrom the group consisting of SEQ ID NO: 112, SEQ ID NO: 113 SEQ ID NO:114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO:123, SEQ ID NO: 124, and SEQ ID NO:
 125. 80. A kit for amplifying apolymorphic marker from a plant comprising in one or more containers, atleast one oligonucleotide primer of claim 78 or
 79. 81. A method forscreening for herbicide resistant and herbicide susceptible plantscomprising amplifying a polymorphic marker in a PCR-based assay usingDNA from said plant, wherein said PCR comprises at least one primercomprising a sequence of SEQ ID NO: 18 or SEQ ID NO:
 19. 82. The methodof claim 81 wherein said plant is Conyza canadensis.
 83. The method ofclaim 81 wherein said PCR-based assay further comprises at least oneother component selected from the group consisting of a DNA polymerase,dNTPs, a primer comprising the sequence of SEQ ID NO: 20 and a primercomprising the sequence of SEQ ID NO:
 21. 84. A method of identifying atherapeutic compound to increase a resistance to herbicides in a plantcomprising: (a) introducing a gene conferring herbicide susceptibilityinto a plant; (b) isolating purified protein from said plant; (c)contacting said protein with a panel of candidate compounds; (d)selecting compounds that bind to said protein; and (e) screening for theability of a selected compound to interfere with herbicidesusceptibility; thereby identifying a therapeutic compound.